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Biomedical subjects

W Koenig

Publications and source records attributed to W Koenig.

At least 37 records · Page 2Linked to original sources
PubMed2001

Leukocyte attack in a 3D human coronary in-vitro model.

OBJECTIVE: The importance of peripheral blood leukocytes for the development of early atherosclerosis and restenosis has confronted cardiologists with classical hematologic issues. Three-dimensional human coronary in-vitro units of leukocyte attack (3DLA-units) open the field for exact studies of leukocyte attack and its subsequent effects on human medial coronary smooth muscle cells (HCMSMC). METHODS: Central part of 3DLA-units are polycarbonate membranes with a pore size of 5 microm that correspond to the internal elastic membrane. Human coronary endothelial cells (HCAEC) were cultured on one side of the membranes, HCMSMC on the other side. Before leukocyte attack expression of adhesion molecules was up-regulated by tumour necrosis factor-alpha (TNF-alpha). Leukocyte attack was mimicked by selective adding of human monocytes (MC), respectively human CD4+-lymphocytes (CD4+-LC) to the HCAEC side of the 3DLA-units. Three-dimensional leukocyte attack units were fixed and stained after a period of 30 min, 1, 2, 3, 4, 6, and 24 h. Cell divisions of HCMSMC were analysed by measuring the uptake of bromodeoxyuridine (BrdU). RESULTS: Monocytes were able to adhere to the endothelial surface, pass through the filter-pores, and penetrate the HCMSMC side of the 3DLA-units. Human CD4+-lymphocytes (CD4+-LC) only attached to the HCAEC side, and no chemotaxis to the HCMSMC side was detected. Proliferation of HCMSMC was increased 2.9-fold (P< 0.001) after selective MC-attack and 3.5-fold after selective MC-attack and TNF-alpha stimulus. No significant increase was found after selective CD4+-LC attack, a significant increase (2.1-fold; P < 0.001) was seen after selective CD4+-LC attack and TNF-alpha, stimulus. CONCLUSIONS: Within the given limitations of the model the study emphasizes a predominance of MC in comparison to CD4+-LC in the process of adhesion, chemotaxis, and triggered reactive proliferation of co-cultured HCMSMC within the first 24 h after leukocyte attack. 3DLA-units offer an elegant method to study directly the effects of intravascular and intramural treatment strategies.

CD4-Positive T-Lymphocytes↗
PubMed2001

Current infection with Helicobacter pylori, but not seropositivity to Chlamydia pneumoniae or cytomegalovirus, is associated with an atherogenic, modified lipid profile.

Infectious agents may be involved in atherothrombogenesis. The potential pathogenic pathway, however, remains unclear. We investigated the association between various infectious agents and lipoproteins known to have an atherogenic effect. We recruited 470 healthy blood donors and 238 patients with angiographically proven coronary heart disease (CHD), aged 40 to 68 years. Seropositivity to Chlamydia pneumoniae (CP), chlamydial lipopolysaccharide, and cytomegalovirus (CMV) was determined; infection with Helicobacter pylori (HP) was assessed by using the [(13)C]urea breath test. In all subjects, total cholesterol, high density lipoprotein (HDL) cholesterol, lipoprotein(a), and various apolipoproteins (apos) were determined. In unadjusted analysis, mean HDL cholesterol concentration was significantly decreased in HP-positive healthy subjects (1.36 vs 1.44 mmol/L, P=0.006) compared with HP-negative subjects. The HDL cholesterol to total cholesterol ratio was significantly decreased in HP-positive (0.259 vs 0.276, P=0.01) and CP-seropositive (0.266 vs 0.280, P=0.04) healthy subjects compared with (sero)negatives. Mean apoAI levels were significantly lower in HP-positive healthy subjects (1.46 vs 1.51 g/L, P=0.03) and in CMV-positive healthy subjects (1.47 vs 1.52 g/L, P=0.01) compared with (sero)negative subjects. After multivariable adjustment by means of linear regression analysis, only the association between HP infection and decreased HDL cholesterol (P=0.002), decreased HDL cholesterol to total cholesterol ratio (P:=0.005), decreased apoAI (P=0.02), and increased apoB (P=0.02) persisted and remained significant. There was no independent association between other lipoproteins and serological markers of CP or CMV infection. Current infection with HP, but not seropositivity to CP or CMV, was associated with an atherogenic, modified lipid profile. These lipid alterations could explain, at least in part, the reported weak association between chronic HP infection and atherosclerotic diseases.

Adult↗
PubMed2001

Plasma fibrin D-dimer levels and risk of stable coronary artery disease: results of a large case-control study.

Increased levels of fibrin D-dimer are indicative of a hypercoagulable state, as found in acute coronary syndromes. Few well-controlled studies have assessed D-dimers in patients with stable coronary artery disease (CAD). We measured levels of D-dimers (in ng/mL by enzyme-linked immunosorbent assay) in 312 patients with angiographically proved CAD and stable angina pectoris and in 477 age- and sex-matched healthy blood donors. Demographic characteristics were assessed by a standardized questionnaire, and a complete lipid profile was performed for all subjects. In addition, a variety of other markers of hemostasis and inflammation were measured. The distribution of D-dimer levels was skewed to the right, and plasma median levels were higher in cases than in controls (median: 11.2 vs 2.8 ng/mL; P<0.001). In controls, correlations of D-dimer were found with fibrinogen, plasma viscosity, and interleukin-6. In logistic regression analysis, the age- and sex-adjusted odds ratio (OR) for the presence of CAD was 2.6 (95% confidence interval [CI], 1.9 to 3.5) when the highest quartile of the D-dimer distribution was compared with the combined lower 3 quartiles. The OR did not change appreciably after controlling for nonlipid risk factors (OR, 2.7; 95% CI, 1.9 to 3.9) and remained significant after further adjustment for other hemostatic parameters (OR, 2.4; 95% CI, 1.7 to 3.3) and markers of inflammation (OR, 2.1; 95% CI, 1.5 to 2.9). Plasma D-dimer levels are strongly and independently associated with the presence of CAD in patients with stable angina pectoris. These results support the concept of a contribution of intravascular fibrin to atherothrombogenesis.

Adult↗
PubMed2001

Effects of air pollution on blood pressure: a population-based approach.

OBJECTIVES: This analysis assessed the association between blood pressure, meteorology, and air pollution in a random population sample. METHODS: Blood pressure measurements of 2607 men and women aged 25 to 64 years who participated in the Augsburg Monitoring of Trends and Determinants in Cardiovascular Disease survey were analyzed in association with 24-hour mean concentrations of air pollutants. RESULTS: During the air pollution episode in Europe in January 1985, an association between blood pressure and air pollution was observed, which disappeared after adjustment for meteorology. Continuous concentrations of total suspended particulates and sulfur dioxide were associated with an increase in systolic blood pressure of 1.79 mm Hg (95% confidence interval [CI] = 0.63, 2.95) per 90 micrograms/m3 total suspended particulates and 0.74 mm Hg (95% CI = 0.08, 1.40) per 80 micrograms/m3 sulfur dioxide. In subgroups with high plasma viscosity levels and increased heart rates, systolic blood pressure increased by 6.93 mm Hg (95% CI = 4.31, 9.75) and 7.76 mm Hg (95% CI = 5.70, 9.82) in association with total suspended particulates. CONCLUSIONS: The observed increase in systolic blood pressure associated with ambient air pollution could be related to a change in cardiovascular autonomic control.

Adult↗
PubMed2001

C-reactive protein: risk assessment in the primary prevention of atherosclerotic disease. Has the time come for including it in the risk profile?

About half of patients presenting with myocardial infarction do not have the "classic" risk factors. This has stimulated a search for other factors that may be responsible and, when present, may help to predict which patients are at greatest risk for myocardial infarction and other cardiovascular events. With improved understanding of the pathogenesis of ischemic cardiovascular disease, we have gleaned new insights into potential markers of underlying atherosclerosis and cardiovascular risk. In recent years, data suggesting that certain markers of inflammation--both systemic and local--play a key role in the development and progression of atherosclerosis, and in its final clinical complications have accumulated. Specifically, elevated levels of one systemic marker of inflammation, C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease events. Among several markers of systemic inflammation, CRP shows the strongest associations with vascular events, and the addition of CRP to total cholesterol dramatically improves risk prediction. CRP fulfils most of the requirements needed to serve as a new risk factor, but still several issues await further confirmation and clarification before this marker can ultimately be included in the routine risk profile. Moreover, potentially important associations have been established between elevated CRP levels and increased efficacy of established therapies, in particular lipid-lowering therapy with statins; CRP testing may enable us to tailor expensive cardiovascular medication to the individual patient. Such an improved prescription strategy might be especially valuable in the primary care setting where the absolute cardiovascular risk is considerably lower compared to that in secondary prevention.

Biomarkers↗
PubMed2001

C-reactive protein and atherosclerosis: quo vadis?

In recent years numerous studies have demonstrated a direct association between elevated levels of C-reactive protein (CRP) and future risk of cardiovascular disease. An intriguing question is whether CRP represents just a sensitive marker of systemic inflammation, a process known to play an important role in atherothrombogenesis, or whether it may contribute actively to atherosclerotic lesion formation. In this paper we summarize the current evidence for an involvement of CRP in atherogenesis and we speculate about potential therapeutic implications these observations might have.

Biomarkers↗
PubMed2000

The impact of diabetes mellitus on survival after myocardial infarction: can it be modified by drug treatment? Results of a population-based myocardial infarction register follow-up study.

AIMS/HYPOTHESIS: Mortality of diabetic patients after myocardial infarction remains high despite recent improvement in their management. This study population-based evaluates the impact of cardiovascular drug therapy on mortality within 28 days and during 5-year follow-up in diabetic compared with non-diabetic patients. METHODS: Using the MONICA Augsburg register from 1985 to 1992, 2210 inpatients with incident Q-wave myocardial infarction aged 25-74 years were included, of whom 468 had diabetes. Primary end point was mortality within 28 days and over 5 years. General linear model procedures were used for age-adjustment, controlling for sex, and testing significance; hazard risk ratios were calculated using multivariable Cox proportional hazards model procedures. RESULTS: During the 5-year follow-up, 598 subjects died (396 diabetic, 202 non-diabetic). The mortality rate within 28 days was 12.6% in diabetic patients (women 18.0%, men 9.9%) and 7.3% in non-diabetic patients (p = 0.001). Mortality in diabetic patients over 5 years was increased by 64% (95% confidence interval 1.39-1.95) compared with non-diabetic patients. This was considerably reduced (p < 0.001) in patients treated with thrombolytic drugs (risk ratio: diabetes 0.57, no diabetes 0.65) and with beta blockers (0.62 and 0.64) and antiplatelets (0.76 and 0.74) at hospital discharge. Mortality of diabetic patients treated with these drugs was reduced to that of non-diabetic patients without such treatment (risk ratio 1.01 to 1.27; p > 0.1). CONCLUSION/INTERPRETATION: Diabetic patients after myocardial infarction are at particularly high risk of dying, but benefit clearly from treatment with thrombolytics, beta blockers and antiplatelets. This study does not, however, allow any inferences to be drawn for treatment with angiotensin converting enzyme inhibitors or the impact of left ventricular function.

Adrenergic beta-Antagonists↗
PubMed2000

Seropositivity to chlamydial lipopolysaccharide and Chlamydia pneumoniae, systemic inflammation and stable coronary artery disease: negative results of a case-control study.

OBJECTIVES: We investigated the association between seropositivity to chlamydial lipopolysaccharide (cLPS) or Chlamydia pneumoniae (CP) and angiographically documented coronary artery disease (CAD), and we examined the relationship between serostatus and markers of systemic inflammation. BACKGROUND: The potential contribution of CP to atherogenesis is still a matter of debate, and inflammation has been suggested to represent the link between infection and atherosclerotic disease. METHODS: Subjects age 40 to 68 years were recruited for this case-control study between October 1996 and November 1997: 312 patients with at least one coronary stenosis >50% and 479 age- and sex-matched blood donors without manifest CAD or history of angina. Antibodies against cLPS and CP, C-reactive protein (CRP), fibrinogen, plasma viscosity, leukocytes and neutrophils were determined. The study had a power of >80% to detect an odds ratio (OR) of 1.55 or above for the prevalence of immunoglobulin (IgG) antibodies against cLPS at a significance level of alpha = 0.05. RESULTS: Prevalence of IgG antibodies against cLPS was not different between cases and controls (61% vs. 62%; p = 0.7). The adjusted OR for the presence of CAD given positive IgG serostatus against cLPS was 0.9 (95% CI; 0.6 to 1.3). Similarly, no difference in the prevalence of IgG antibodies against CP was seen (88% vs. 87%; p = 0.6); the adjusted OR was 1.0 (95% CI; 0.6 to 1.6). Markers of inflammation did not show any statistically significant difference between cLPS seropositives and seronegatives. CONCLUSIONS: Our results indicate no strong association between CP and CAD, and increased systemic inflammation in patients with CAD does not seem to be due to seropositivity to cLPS or CP.

Adult↗
PubMed2000

Association between plasma viscosity and all-cause mortality: results from the MONICA-Augsburg Cohort Study 1984-92.

Several studies have reported a strong association between various markers of the acute-phase response and death from cardiovascular diseases and all-cause mortality. Inflammation at a low level of intensity may be a common phenomenon associated with the majority of causes of death owing to chronic diseases. We sought to investigate the association of plasma viscosity with all-cause mortality in a cohort of apparently healthy men. The study population consisted of 964 men aged 45-64 years at entry, randomly selected from the general population and taking part in the first MONICA-Augsburg survey 1984-85. The main outcome measure was all-cause mortality. During 8 years of follow-up, there were 81 deaths (37 cardiovascular deaths, 23 deaths from cancer and 21 deaths from other causes). There was a strong positive and statistically significant age-adjusted relationship between plasma viscosity and all-cause mortality. The relative risk of death for a one standard deviation increase in plasma viscosity (0.070 mPa/s) was 1.45 [95% confidence interval (CI) 1.19-1.76]. After further adjusting for smoking, total cholesterol, body mass index, blood pressure and education, a relative risk of 1.41 (95% CI 1.14-1.74) resulted. Other risk variables had only negligible confounding effects. The relative risk of the median of the top quintile of the plasma viscosity distribution compared with the median of the bottom quintile, computed from the adjusted model, was 2.68 (95% CI 1.63-4.42). These findings suggest that plasma viscosity may have considerable potential to predict death from all causes in middle-aged men.

Acute-Phase Reaction↗
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

Exercise and thrombosis.

Long-term moderate or strenuous physical activity is associated with a considerable reduction in cardiovascular morbidity and mortality. This article reviews the evidence to suggest that part of the effect is mediated through the effects on thrombogenic factors. Fibrinogen has been convincingly shown to be an independent cardiovascular risk factor. Other hemostatic and fibrinolytic parameters that are predictive of coronary events include factor VII, platelet hyperreactivity, plasminogen activator inhibitor-1, and tissue-plasminogen activator. The effects of exercise on fibrinogen have been studied intensively. One randomized, controlled trial, two other intervention studies and a large number of population-based cross-sectional studies have consistently found an inverse relationship between various measures of sport activity or leisure activity and plasma levels of fibrinogen. The magnitude of the effect might be associated with a sizeable reduction in major coronary events. Relatively few data are available on endurance exercise and markers of the fibrinolytic system. Acute exercise leads to a transient activation of the coagulation system, which is accompanied by an increase in the fibrinolytic capacity in healthy subjects. However, patients with ischemic heart disease, who cannot increase their fibrinolytic potential, may be at considerable risk for acute ischemic events if they are exposed to unaccustomed strenuous physical exertion. It is concluded that physical activity has profound effects on thrombogenic factors and that these mechanisms could contribute to its beneficial cardiovascular effects.

Coronary Thrombosis↗
PubMed2000

C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis.

Infiltration of monocytes into the arterial wall is an early cellular event in atherogenesis. Recent evidence shows that C-reactive protein (CRP) is deposited in the arterial intima at sites of atherogenesis. In this study, we demonstrate that CRP deposition precedes the appearance of monocytes in early atherosclerotic lesions. CRP is chemotactic for freshly isolated human blood monocytes. A specific CRP receptor is demonstrated on monocytes in vitro as well as in vivo, and blockage of the receptor by use of a monoclonal anti-receptor antibody completely abolishes CRP-induced chemotaxis. CRP may play a major role in the recruitment of monocytes during atherogenesis.

Antibodies, Monoclonal↗
PubMed2000

Association between C-reactive protein and features of the metabolic syndrome: a population-based study.

OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence of diabetes and hypertension were assessed in 747 men and 956 women aged 18-89 years who were participating in the population-based National Health and Nutrition Survey, which was carried out in former West Germany in 1987-1988. RESULTS: There was a statistically significant positive crude correlation between C-reactive protein and TC (R = 0.19), TG (R = 0.29), BMI (R = 0.32), glucose (R = 0.11), and uric acid (R = 0.14) (all P < 0.0001). A negative correlation was found between C-reactive protein and HDL cholesterol (R = 0.13, P < 0.0001). The age-adjusted geometric means of C-reactive protein concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P < 0.0001). CONCLUSIONS: The data suggest that a variety of features of the metabolic syndrome are associated with a systemic inflammatory response.

Adolescent↗
PubMed2000

Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population.

BACKGROUND: : Increased values of C-reactive protein (CRP), the classical acute phase protein, within the range below 5 mg/L, previously considered to be within the reference interval, are strongly associated with increased risk of atherothrombotic events, and are clinically significant in osteoarthritis and neonatal infection. METHODS: : A robust new polyclonal-monoclonal solid- phase IRMA for CRP was developed, with a range of 0.05-10.0 mg/L. RESULTS: : Plasma CRP values in general adult populations from Augsburg, Germany (2291 males and 2203 females; ages, 25-74 years) and Glasgow, Scotland (604 males and 650 females; ages, 25-64 years) were very similar. The median CRP approximately doubled with age, from approximately 1 mg/L in the youngest decade to approximately 2 mg/L in the oldest, and tended to be higher in females. CONCLUSION: : This extensive data set, the largest such study of CRP, provides valuable reference information for future clinical and epidemiological investigations.

Adult↗
PubMed1999

Infection with Helicobacter pylori is not a major independent risk factor for stable coronary heart disease: lack of a role of cytotoxin-associated protein A-positive strains and absence of a systemic inflammatory response.

BACKGROUND: There is controversy about the association between Helicobacter pylori infection and manifestations of coronary heart disease (CHD), the potential role of the more virulent H pylori strains, and whether or not a positive serostatus is related to increased levels of markers of systemic inflammation. METHODS AND RESULTS: We assessed the prevalence of an infection with H pylori and in particular the anti-cytotoxin-associated protein A (CagA) antibody response of the more virulent strains expressing CagA in 312 patients with stable CHD and in 479 control subjects. Serological prevalence of H pylori infection (IgG titer) was significantly higher in patients than in control subjects after adjustment for age and sex (44.2% versus 31.3%, P<0.001). After adjustment for various covariates in multiple logistic regression, the odds ratio (OR) for CHD was 1.3 (95% CI, 0.9 to 1.9) given a positive IgG serostatus. The prevalence of CagA-positive strains was 27.9% in patients and 21.7% in control subjects (P=0.076 adjusted for age and sex). The OR for CHD in the fully adjusted model was 1.1 (95% CI, 0.7 to 1.7). None of the inflammatory markers (C-reactive protein, fibrinogen, plasma viscosity, or leukocytes) was significantly different according to serostatus. CONCLUSIONS: In this large case-control study, the association of H pylori infection with stable CHD was strongly reduced and was no longer statistically significant after controlling for potential confounders. We also found no independent association between the more virulent strains and CHD. In addition, a positive serostatus was not associated with a systemic inflammatory response. Thus, these data do not support the hypothesis that infection with H pylori might be a major risk factor for stable CHD.

Aged↗