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H Schunkert

Publications and source records attributed to H Schunkert.

At least 19 recordsLinked to original sources
PubMed2005

Failure to achieve recommended LDL cholesterol levels by suboptimal statin therapy relates to elevated cardiac event rates.

OBJECTIVES: The majority of patients with myocardial infarction (MI) and hypercholesterolaemia does not achieve guideline recommended low-density lipoprotein cholesterol (LDL) levels. Suboptimal dosages of statins explain this dilemma in most patients. DESIGN AND SETTING: We evaluated the relationship between statin treatment quality (optimal: LDL<115 mg/dl, suboptimal: LDL>/=115 mg/dl, no statin therapy despite hypercholesterolaemia) and the subsequent incidence of coronary events (coronary death, nonfatal MI, bypass surgery) over a 30 months follow-up in a large cohort of post MI patients with hypercholesterolaemia (n=2045). Analysis was performed in a nested case-control manner comparing 173 cases with a coronary event and 346 matched controls. RESULTS: Patients who developed a coronary event were treated optimally in 11.0%, suboptimally in 43.4% (p<0.05 vs. optimal treatment) and were untreated in 45.7% (p<0.001 vs. optimal treatment). Respective numbers in event-free patients were 21.4%, 47.7%, and 30.9%. After adjustment for most potential confounders, including all cardiovascular risk factors and medication, the relative risk of future non-fatal MI and coronary death associated with a suboptimal statin treatment was 2.02 (95% CI 1.04 to 4.18) compared to optimal statin treatment. Moreover, the statin equivalent dose in optimally treated individuals was significantly higher than in suboptimally treated individuals (0.85+/-0.03 vs. 0.78+/-0.02, p<0.05). CONCLUSION: In this community-based study, a lipid lowering therapy with statins into the recommended target range of LDL levels may be associated with decreased cardiovascular risk compared to a statin therapy without titrating the LDL level below 115 mg/dl. Thus, the quality of statin treatment was identified as an independent predictor of coronary events in post MI patients.

Aged↗
PubMed2005

ACE inhibitors and angiotensin II receptor antagonists.

The biological actions of angiotensin II (ANG), the most prominent hormone of the renin-angiotensin-aldosterone system (RAAS), may promote the development of atherosclerosis in many ways. ANG aggravates hypertension, metabolic syndrome, and endothelial dysfunction, and thereby constitutes a major risk factor for cardiovascular disease. The formation of atherosclerotic lesions involves local uptake, synthesis and oxidation of lipids, inflammation, as well as cellular migration and proliferation--mechanisms that may all be enhanced by ANG via its AT1 receptor. ANG may also increase the risk of acute thrombosis by destabilizing atherosclerotic plaques and enhancing the activity of thrombocytes and coagulation. After myocardial infarction, ANG promotes myocardial remodeling and fibrosis, and its many pathological mechanisms deteriorate the prognosis of these high-risk patients in particular. Therapeutically, inhibitors of the angiotensin I-converting enzyme (ACEI) and AT1 receptor blockers (ARB) are available to suppress the generation and cellular signaling of ANG, respectively. Despite major differences in the efficacy of ANG suppression and the modulation of other hormones and receptors, both classes of drugs are generally effective in attenuating numerous pathomechanisms of ANG in vitro, and in diminishing the development of atherosclerotic lesions and restenosis after angioplasty in various animal models. In clinical therapy, ACEI and ACE are well-tolerated antihypertensive drugs that also improve the prognosis of heart failure patients. After myocardial infarction and in stable coronary heart disease, ACEI have been shown to reduce mortality in a manner independent of hemodynamic alterations. However, there is little evidence that inhibitors of the RAAS may be effective against arterial restenosis, and a possible benefit of these substances compared to other antihypertensive drugs in the primary prevention of coronary heart disease in hypertensive patients is still a matter of debate, possibly depending on the specific substance and condition being investigated. As such, the general clinical efficacy of ACEI and ARB may be due to a positive influence on hemodynamic load, vascular function, myocardial remodeling, and neuro-humoral regulation, rather than to a direct attenuation of the atherosclerotic process. Further therapeutic advances may be achieved by identifying optimum drugs, patient populations, and treatment protocols.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

[Anticoagulation for secondary prevention: which drug in which situation?].

Thromboembolic events are a major complication of cardiovascular diseases. Secondary prevention of thromboembolic complications can be achieved by anticoagulation with heparin or vitamin-K-antagonists. A new class of direct thrombin inhibitors has been recently introduced into clinical medicine. Clinical studies have demonstrated theses agents to be comparable in efficacy for prophylaxis of venous thromboembolism. However, the results of ongoing trials are awaited in helping to define the place of direct thrombin inhibitors in secondary prevention. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines and glycoprotein IIb/IIIa inhibitors represents an important addition to the physician's armamentarium. Due to the increased risk of major bleeding, for each patient the decision of anticoagulation and antiplatelet therapy must be tightly correlated to the individual benefit-risk ratio.

Anticoagulants↗
PubMed2005

BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy.

BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi). BNP increased in subjects with diastolic dysfunction (mean 20.3+/-4.7 pg/ml vs. control 9.6+/-0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3+/-49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2+/-23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7+/-1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%). Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy.

Adult↗
PubMed2005

[Distribution, determinants and reference values of left ventricular parameters in the general population--results of the MONICA/KORA echocardiography studies].

For successful fighting against the burden of cardiovascular disease in the community a comprehensive knowledge about the prevalence and the impact of underlying risk factors is important. The present paper summarises some studies undertaken on more than 2000 persons from the MONICA/KORA-studies (parts of S1 and S3) where left ventricular mass (LVM) and other left ventricular parameters were determined by echocardiography. We especially investigated the associations of LVM with blood pressure and obesity. A special focus was on sex-specific factors in the determination of LVM and the influence of different indices of body size when normalising LVM. It could be shown that hypertension and obesity are major determinants of LV hypertrophy. Especially women with both hypertension and obesity on showed a high prevalence of concentric hypertrophy, significantly more than men. We also showed that the prevalence of LV hypertrophy in a representative sample of the general population (25 to 74 years) is 17.5 % for men, and 18.5 % for women. This underscores the need for primary and secondary prevention regarding the development of LV hypertrophy. Finally, our data in a selected group of normal subjects (reference sample) may be used for the development of reference values for left ventricular parameters in the general German population.

Adult↗
PubMed2005

Cardiovascular phenotypes and functional parameters in the general population--results of the MONICA/KORA studies.

The MONICA/KORA surveys are characterized by a careful and broad investigation of multiple cardiovascular phenotypes. Particularly, repeated blinded measurements of blood pressure, comprehensive echocardiographic and electrocardiographic evaluations as well as differentiation between fat and fat-free body mass have led to manifold innovative observations. Specifically, genetic and serological markers of the renin angiotensin system could be associated with high blood pressure and left ventricular hypertrophy. The same applies to the importance of parameters of body composition as obesity and muscular mass. Moreover, the prevalence of heart failure in the general population could be determined for the first time in Germany. Additionally, the prevalence of left ventricular systolic and diastolic dysfunction could be obtained in the region of the survey, exemplarily for the Federal Republic of Germany. Finally, the surveys of the population random sample were used to define normal serum levels of natriuretic peptides. In summary, the evaluation of cardiovascular phenotypes in the MONICA/KORA surveys resulted in a -- in the European region unique -- documentation of cardiovascular functional parameters in the general population. Moreover, multiple epidemiological observations as to pathophysiologically relevant topics of heart and vascular diseases could be studied in extraordinary details.

Adult↗
PubMed2004

Interactions between the sympathetic nervous system and the cardiac natriuretic peptide system.

The sympathetic nervous system (SNS) and the cardiac natriuretic peptide system (NPS) are fundamentally important neurohumoral systems for cardiovascular regulation. Their mutual interactions have been subject to numerous experimental and human studies. In the current manuscript, results from in vivo and in vitro studies will be reviewed with a focus on sympathetic outflow on the control of natriuretic peptide release.

Adrenergic beta-Antagonists↗
PubMed2004

KCNJ11 polymorphisms and sudden cardiac death in patients with acute myocardial infarction.

PURPOSE: Patients with an acute myocardial infarction (AMI) are of high risk to develop ischemia-induced ventricular arrhythmias, leading to sudden cardiac death (SCD) in about one third of all AMI patients. The individual susceptibility to ischemia-induced arrhythmias may be modified by polymorphisms in genes encoding ion channels. The cardiac ATP-dependent potassium channel (K(ATP)) current is generated by ion channels encoded by the KCNJ11 gene and the SUR2a gene. Opening of the K(ATP) channel during ischemia results in action potential shortening in various studies and may therefore influence the outcome of AMI patients. METHODS: Using a three-primer strategy, we sequenced the complete coding and adjacent 5' and 3' sequences of the intronless KCNJ11 gene (1.3 kb) prospectively in two groups. Patients of group 1 (n = 84) survived three or more transmyocardial infarctions without developing any ventricular arrhythmias. Patients of group 2 died suddenly from their first myocardial infarction (n = 86), most of them witnessed SCDs. RESULTS: We identified a total of six known polymorphisms (K23E, A190A, L267V, L270V, I337V, and K281K) and two new polymorphisms (L267L, 3'UTR +62 G/A). The allele, genotype, and haplotype frequencies did not differ between the two groups. All polymorphisms were found to be in Hardy-Weinberg equilibrium. In addition, we identified two novel missense mutations in a highly conserved region of the gene in two patients of group 2 (P266T and R371H) with yet unknown functional consequences. CONCLUSION: In this study of AMI patients, SCD was not related to polymorphisms in the KCNJ11 gene.

Aged↗
PubMed2003

[Epidemiology of left ventricular systolic dysfunction in the general population of Germany: results of an echocardiographic study of a large population-based sample].

The prevalence of left ventricular systolic dysfunction (LVSD) in the general population is poorly defined. Specifically, the number of asymptomatic individuals with LVSD and, thus, the most appropriate strategy to identify and treat such subjects is still unknown. Therefore, the aim of this study was to document LV dysfunction in a middle-aged (25 to 75 years, mean 51.8+/-13.8) population - based sample in Germany (MONICA Augsburg, n=1678; echocardiography technically adequate n=1418) by M-mode and 2D-echocardiography and to analyze the importance of predisposing contributors. The overall prevalence of an ejection fraction (EF) less than 48% (mean minus 2 SD=LVSD) was 2.3% (n=33), with a slightly higher rate in men than in women (2.8% vs 1.9%, n.s.). LVSD rate increased with age: from 1.5% in individuals younger than 40 years to 4.0% among those older than 60 years of age (p<0.05). Of 33 participants with reduced left ventricular systolic function, 20 presented with at least one cardiovascular disease. The most frequent diagnoses were arterial hypertension, obesity and coronary heart disease. Only 13 subjects (0.9%) of the study population were asymptomatic without a history of cardiovascular disease. Furthermore, only 6 subjects (0.4%, 4 male) in this population presented with a moderate impairment of LV function (EF of 30 to 40%) and only 1 subject (0.07%, male) had severe LVSD (EF less than 30%). Almost all subjects with an EF less than 40% (6 of 7 individuals) had a known history of cardiovascular disease. In conclusion, LVSD is a relatively common finding in the general population. However, severe LVSD is rare in subjects without any concomitant cardiovascular disease. Thus, echocardiographic screening cannot be recommended in the unselected, middle-aged population to identify such patients.

Adult↗
PubMed2003

Prevalence of left ventricular diastolic dysfunction in the community. Results from a Doppler echocardiographic-based survey of a population sample.

AIMS: The prevalence of left ventricular diastolic abnormalities in the general population is largely unclear. Thus, the aim of this study was, firstly, to identify abnormal diastolic function by echocardiography in an age-stratified population-based European sample (MONICA Augsburg, n=1274, 25 to 75 years, mean 51+/-14) and, secondly, to analyse clinical and anthropometric parameters associated with diastolic abnormalities. METHODS AND RESULTS: The overall prevalence of diastolic abnormalities, as defined by the European Study Group on Diastolic Heart Failure (i.e. age dependent isovolumic relaxation time (92-105 ms) and early (E-wave) and late (A-wave) left ventricular filling (E/A-ratio, 1-0.5)) was 11.1%. When only subjects treated with diuretics or with left atrial enlargement were considered (suggesting diastolic dysfunction) the prevalence was 3.1%. The prevalence of diastolic abnormalities varied according to age: from 2.8% in individuals aged 25-35 years to 15.8% among those older than 65 years (P<0.01). Significantly higher rates of diastolic abnormalities were observed in men as compared to women (13.8% vs 8.6%, P<0.01). Independent predictors of diastolic abnormalities were arterial hypertension, evidence of left ventricular (LV) hypertrophy, and coronary artery disease. Interestingly, in the absence of these predisposing conditions, diastolic abnormalities (4.3%) or diastolic dysfunction (1.1%) were rare, even in subjects older than 50 years of age (4.6%) and (1.2%), respectively. In addition to these factors, diastolic dysfunction was related to high body mass index, high body fat mass, and diabetes mellitus. CONCLUSION: The prevalences of diastolic abnormalities and diastolic dysfunction are higher than that of systolic dysfunction and are increased (despite age-dependent diagnostic criteria) in the elderly. However, in the absence of risk factors for diastolic abnormalities or diastolic dysfunction, namely LV hypertrophy, arterial hypertension, coronary artery disease, obesity and diabetes the condition is rare even in elderly subjects. These data allow speculation on whether diastolic heart failure may be prevented by improved implementation of measures directed against predisposing conditions.

Adult↗