Search PubMed⌕ Search

Biomedical subjects

G Egger

Publications and source records attributed to G Egger.

At least 37 records · Page 2Linked to original sources
PubMed2000

Influence of endurance exercise on respiratory muscle performance.

PURPOSE: During high-intensity, exhaustive, constant-load exercise above 85% of maximal oxygen consumption, the diaphragm of healthy subjects can fatigue. Although a decrease in trans-diaphragmatic pressure is the most objective measure of diaphragmatic fatigue, possible extra-diaphragmatic muscle fatigue would not be detected by this method. The aim of the present study was to investigate the impact of exhaustive, constant-load cycling exercise at different intensities on global respiratory performance determined by the time to exhaustion while breathing against a constant resistance. METHODS: Ten healthy, male subjects performed an exhaustive cycling endurance test at 65, 75, 85, and 95% of peak oxygen consumption (VO2peak). Before cycling (to) as well as at 10 min (t10) and 45 min (t45) after cycling, respiratory performance was determined. RESULTS: Breathing endurance was equivalently reduced after exhaustive cycling at either 65% (8.4 +/- 4.1 min [t0] vs 3.9 +/- 2.8 min [t10]), 75% (9.9 +/- 6.1 vs 4.4 +/- 2.8 min), 85% (9.3 +/- 6.0 vs 3.8 +/- 2.9 min), or 95% VO2peak (8.5 +/- 5.1 vs 4.0 +/- 2.5 min) and, therefore, was independent of exercise intensity. CONCLUSION: This result contradicts previous findings, possibly due to the fact that extra-diaphragmatic muscles are tested in addition to the diaphragm during resistive breathing.

Adult↗
PubMed2000

Distinct risk profiles of early and advanced atherosclerosis: prospective results from the Bruneck Study.

Most epidemiological surveys on risk factors of atherosclerosis were cross-sectional in design and did not consider the existence of pathologically distinct processes. The Bruneck Study is a prospective survey in the general community (age range, 40 to 79 years). The baseline examination and first reevaluation were performed in the summers of 1990 and 1995 (participation, 92%; follow-up, 96%). Carotid atherosclerosis was monitored with high-resolution duplex ultrasound. Early (incidence and/or extension of nonstenotic lesions) and advanced (incidence and/or progression of stenosis >40%) stages of atherogenesis were differentiated. The risk profile of early atherogenesis consists of traditional risk factors, such as hypertension, hyperlipidemia, and cigarette smoking (pack-years), supplemented by a variety of less well-established risk conditions, including high body iron stores, hypothyroidism, microalbuminuria, and high alcohol consumption. In contrast, the risk profile of advanced atherogenesis includes markers of enhanced prothrombotic capacity, attenuated fibrinolysis, and clinical conditions known to interfere with coagulation: high fibrinogen, low antithrombin, factor V Leiden mutation, lipoprotein(a) >0.32 g/L, high platelet count, cigarette smoking, and diabetes. Hyperlipidemia and hypertension were of only minor relevance. These findings, along with the epidemiological features of advanced atherogenesis and emergence of an elevated fibrin turnover, suggest atherothrombosis to be a key mechanism in the development of advanced stenotic atherosclerosis. Supplementary 6-category logistic regression models illustrate the changing association between major risk predictors and atherosclerosis of increasing severity and substantiate appropriateness of the 40% threshold applied for the definition of advanced stenotic atherosclerosis. Atherosclerosis is a heterogeneous process that subsumes etiologically and epidemiologically distinct disease entities. The multifactorial etiology of atherosclerosis, which goes far beyond the traditional risk factors, has not yet achieved adequate attention in clinical practice and disease prevention.

Adult↗
PubMed2000

The affinity of MCF7 breast cancer cells to hyaluronan substrates of different molecular weight and concentrations in an in vitro model.

The affinity of MCF7 breast cancer cells to hyaluronan (HA) was investigated in an in vitro model. The cells form a tightly adhering monolayer on native HA with a concentration of 5 mg/ml. On native HA at higher concentrations the cells reduce their adhesion to the substrate in favor of increased intercellular bonds, resulting in a cluster-like aggregate that tends to detach from the substrate. Aggregate formation is accomplished after 12 h incubation. The phenomenon is independent of the CD44 receptor. Degradation of native HA by hyaluronidase abolishes aggregate formation even at high HA concentrations in favor of formation of a firmly adhering monolayer. This model may help to understand tumor spread on HA tissue structures and may explain therapy successes with hyaluronidase in tumor patients.

Adenocarcinoma↗
PubMed1999

Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study.

BACKGROUND: Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a) [Lp(a)], depending on Lp(a) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a) [apo(a)] isoforms. Epidemiological studies may contribute to assessment of the relevance of these findings in the general population. METHODS AND RESULTS: This study prospectively investigated the association between Lp(a) plasma concentrations, apo(a) phenotypes, and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a random sample population of 826 individuals. We differentiated early atherogenesis (incident nonstenotic atherosclerosis) from advanced (stenotic) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms. Lp(a) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion, with this association being confined to subjects with LDL cholesterol levels above the population median (3.3 mmol/L). Apo(a) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis. In contrast, apo(a) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis, especially when associated with high Lp(a) plasma concentrations (odds ratio, 6.4; 95% CI, 2.8 to 14. 9). CONCLUSIONS: Lp(a) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis. Lp(a) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol. Low-molecular-weight apo(a) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis.

Adult↗
PubMed1999

Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis : clinical significance determined in a follow-up study.

BACKGROUND: Previous work has proved that increased titers of antibodies against heat-shock protein (hsp) 65 are associated with atherosclerotic lesions independently of other established risk factors. The present follow-up study was designed to further scrutinize the association of hsp antibodies and atherosclerosis and evaluate the possible predictive value of these antibodies for the development and/or progression of lesions in the same population. METHODS AND RESULTS: A total of 750 subjects 45 to 74 years old were recruited, and the rate of participation was 93.6%; 58 subjects died between 1990 and 1995. All participants were subjected to determination of serum antibodies against hsp65 and sonography to assess carotid atherosclerotic lesions and evaluate other risk factors, ie, age, sex, body mass index, blood cholesterol, apolipoprotein B, apolipoprotein A, triglycerides, lipoprotein(a), fibrinogen, leukocyte number, antithrombin III, ESR, ferritin, hypertension, smoking, and diabetes mellitus. Our data show that hsp65 antibody titers in the population emerged as highly consistent over a 5-year observation period (r=0.78, P<0.0001). Titers were significantly elevated in subjects with progressive carotid atherosclerosis and correlated with intima/media thickness. Multiple linear regression analysis documented these associations to be independent of age, sex, and other risk factors. Subanalyses revealed a preferential association of hsp65 antibody titers with advanced lesions (odds ratio, 1.42; 95% CI, 1.02 to 1.98; P=0.039). Other risk factors neither confounded nor modified this association. Finally, hsp65 antibody titers significantly predicted the 5-year mortality (hazard ratio, 1.52; 95% CI, 1.14 to 2.03; P<0.001). CONCLUSIONS: These findings indicate a sustained existence of anti-hsp65 antibodies in subjects with severe atherosclerosis, which is predictive for mortality.

Antibodies↗
PubMed1999

Poor response to activated protein C as a prominent risk predictor of advanced atherosclerosis and arterial disease.

BACKGROUND: The potential role of activated protein C (APC) resistance in arterial thrombosis and disease is a matter of ongoing controversy. METHODS AND RESULTS: In the present population-based survey, a random sample of 826 men and women underwent high-resolution duplex ultrasound scanning of the carotid and femoral arteries. Response to APC was expressed in APC ratios. Subjects were tested for the factor V Leiden mutation. The risk of carotid stenosis increased gradually with decreasing response to APC (adjusted OR [95% CI] for a 1-U decrease of response to APC, 1.6 [1. 2 to 2.2]), as did the risk of femoral artery stenosis (1.7 [1.3 to 2.3]) and prevalent cardiovascular disease (1.4 [1.1 to 2.0]). The association between low APC ratio and atherosclerotic vascular disease applied equally to subjects with the factor V Leiden mutation and those without. Our study identified various nongenetic determinants of poor response to APC in the general population, including behavioral, hormonal, and environmental factors. CONCLUSIONS: The present study revealed an independent and gradual association between low response to APC and both advanced atherosclerosis (stenosis) and arterial disease. Resistance to APC due to factor V Leiden mutation was only one facet of this relationship.

Adult↗
PubMed1999

Dissecting obesogenic environments: the development and application of a framework for identifying and prioritizing environmental interventions for obesity.

BACKGROUND: The "obesogenicity" of modern environments is fueling the obesity pandemic. We describe a framework, known as ANGELO (analysis grid for environments linked to obesity), which is a conceptual model for understanding the obesogenicity of environments and a practical tool for prioritizing environmental elements for research and intervention. METHODS: Development of the ANGELO framework. The basic framework is a 2 x 4 grid which dissects the environment into environmental size (micro and macro) by type: physical (what is available), economic (what are the costs), political (what are the "rules"), and sociocultural (what are the attitudes and beliefs). Within this grid, the elements which influence food intake and physical activity are characterized as obesogenic or "leptogenic" (promoting leanness). RESULTS: Application of the ANGELO framework. The ANGELO framework has been piloted at the population level (island communities) to prioritize the settings/sectors for intervention and at the setting level (fast food outlets) to prioritize research needs and interventions. Environmental elements were prioritized by rating their validity (evidence of impact), relevance (to the local context), and potential changeability. CONCLUSIONS: The ANGELO framework appears to be a flexible and robust instrument for the needs analysis and problem identification stages of reducing the obesogenicity of modern environments.

Dietary Fats↗
PubMed1999

Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study.

OBJECTIVES: Focus of the current study was on the significance of bacterial endotoxin, which shows a variety of pro-atherogenic properties and may occur at high concentration in the circulation of infected subjects. BACKGROUND: The possibility of an infectious risk factor in atherogenesis and cardiovascular disease has stimulated research interest, but the nature of such process remains obscure. METHODS: We measured plasma endotoxin levels (LAL assay) in a random population of 516 men and women 50 to 79 years old at the 1990 baseline evaluation (Bruneck Study). End points of this prospective survey were incident (early) atherosclerosis in the carotid arteries as assessed with high-resolution Duplex ultrasound (five-year follow-up rate, 98%) and incident cardiovascular disease (follow-up rate, 100%). RESULTS: Median endotoxin concentration amounted to 14.3 pg/ml (range, 6.0 to 209.2 pg/ml). Subjects with levels beyond 50 pg/ml (90th percentile) faced a threefold risk of incident atherosclerosis (odds ratio [95% confidence interval] 2.9 [1.4-6.3]; p < 0.01). The risk associated with high endotoxin was most pronounced in subjects with chronic infections and in current and ex-smokers. Notably, smokers with low endotoxin levels and nonsmokers did not differ in their atherosclerosis risk, whereas smokers with high levels almost invariably developed new lesions. All findings emerged as independent of vascular risk factors. Similar results were obtained for incident cardiovascular disease. CONCLUSIONS: The current study yields first epidemiologic evidence that endotoxemia constitutes a strong risk factor of early atherogenesis in subjects with chronic or recurrent bacterial infections and a link in the association between cigarette smoking and atherosclerotic disease.

Aged↗
PubMed1999

Abdominal obesity reduction in indigenous men.

OBJECTIVES: To assess the effectiveness of a men's 'waist loss' program over one year in Indigenous men. DESIGN: Pre-and post-test measurements of 47 Indigenous men on four island groups in the Torres Strait region of Northern Australia involved in a version of the 'GutBuster' program, modified by and for Indigenous men. RESULTS: Weight, waist and hip size of 47 men, and body fat estimated from electrical impedence measures of 27 men, were compared at baseline, after approx 2 months, approx 6 months and approx one year. Average weight loss was 3.3 kg (3.5%), and waist loss 4.0 cm (3.5%). The average percentage decrease in fat mass (FM) was 10.8%. An environmental audit technique highlighted modifications needed to the environment to assist behaviour change. CONCLUSIONS: Education-behaviour change interventions of this kind may offer opportunities for health improvements in Indigenous men.

Abdomen↗
PubMed1999

TARPARE: a method for selecting target audiences for public health interventions.

OBJECTIVE: This paper presents a model to assist the health promotion practitioner systematically compare and select what might be appropriate target groups when there are a number of segments competing for attention and resources. METHOD: TARPARE assesses previously identified segments on the following criteria: T: The Total number of persons in the segment; AR: The proportion of At Risk persons in the segment; P: The Persuability of the target audience; A: The Accessibility of the target audience; R: Resources required to meet the needs of the target audience; and E: Equity, social justice considerations. The assessment can be applied qualitatively or can be applied such that scores can be assigned to each segment. Two examples are presented. CONCLUSIONS: TARPARE is a useful and flexible model for understanding the various segments in a population of interest and for assessing the potential viability of interventions directed at each segment. The model is particularly useful when there is a need to prioritise segments in terms of available budgets. IMPLICATIONS: The model provides a disciplined approach to target selection and forces consideration of what weights should be applied to the different criteria, and how these might vary for different issues or for different objectives. TARPARE also assesses segments in terms of an overall likelihood of optimal impact for each segment. Targeting high scoring segments is likely to lead to greater program success than targeting low scoring segments.

Health Promotion↗
PubMed1999

Plasma glucose within the normal range is not associated with carotid atherosclerosis: prospective results in subjects with normal glucose tolerance from the Bruneck Study.

OBJECTIVE: There is substantial evidence that glucose intolerance is associated with an increased risk of cardiovascular disease. However, it is not well established whether plasma glucose is independently related to atherosclerosis when glucose tolerance is normal and, if so, to which stage of the complex atherosclerotic process. RESEARCH DESIGN AND METHODS: We prospectively examined the status of carotid arteries in 625 subjects aged 40-79 years who were randomly selected from the general population and had normal glucose tolerance (according to World Health Organization criteria) both at baseline and at 5 years of follow-up. All subjects had high-resolution echo-duplex evaluation of the common and internal carotid arteries (eight regions of interest on both sides) in 1990 and 1995 to detect the change in carotid status over time. The occurrence of new plaques in previously normal segments was termed "incident nonstenotic" or "early atherosclerosis," and the occurrence of stenosis in >40% of previously normal segments was termed "incident stenotic" or "advanced atherosclerosis." In addition, we evaluated the changes in the atherosclerosis score (the sum of all plaques) during the follow-up, and we measured intimal-medial thickening (IMT) in the common carotid artery in 1995. In all subjects, several candidate risk factors were assessed: sex, age, BMI, waist-to-hip ratio, glucose, HbA1c, insulin, urate, lipids, apolipoproteins A1 and B, blood pressure, lipoprotein(a), fibrinogen, antithrombin III, factor V Leiden mutation, ferritin, leukocyte count, smoking, alcohol intake, physical activity, and socioeconomic status. Fasting plasma glucose (FPG), plasma glucose 2 hr after the glucose load (2-h PG), and HbA1c concentrations in 1990 and 1995 were averaged in each subject to obtain an estimate of long-term glucose exposure of the arterial wall. RESULTS: Linear or logistical regression analyses indicated that neither baseline glucose and HbA1c levels nor mean FPG, mean 2-h PG, or mean HbA1c in 1990 and 1995 were independently related to IMT, a 5-year change in the atherosclerotic score, incident nonstenotic (early) atherosclerosis, or incident stenotic (advanced) atherosclerosis. Likewise, subjects with FPG levels above the median and subjects in the new category of "impaired fasting glucose" did not have an increased occurrence or progression of atherosclerosis. All results were consistent before and after adjustment for other vascular risk factors and possible confounders. CONCLUSIONS: These results suggest that plasma glucose levels within the normal range (<7.8 mg/dl both at FPG and 2-h PG) are not independently related to any stage of atherosclerosis.

Adult↗
PubMed1998

Abnormal directed migration of blood polymorphonuclear leukocytes in rheumatoid arthritis. Potential role in increased susceptibility to bacterial infections.

Rheumatoid arthritis (RA) patients are at higher risks of bacterial infection than healthy subjects. Polymorphonuclear leukocytes (PMN) are the first line of nonspecific cellular defence against these infections. We tested the hypothesis that abnormal directed migration of PMN may be one reason for the increased infection rate of RA patients. PMN migration was investigated in 68 peripheral blood samples of 15 RA patients compared with 64 samples of healthy controls in a novel whole blood in vitro membrane filter assay. The migration of PMNs from RA patients and controls was stimulated using the bacterial chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Unstimulated PMN migration of RA patients was increased compared with healthy controls as measured by the following parameters: (a) absolute number of migrant PMNs (1954+/-87 vs. 1238 +/-58 PMN/mm2), (b) percentage of PMNs migrated into the filter (total migration index, TMI) (28.6+/-0.9 vs. 24.0+/-0.8%), (c) the distance half the migrating PMNs had covered (distribution characteristic, DC) (22.6+/-1.1 vs. 16.1+/-0.6 mm) and (d) the product of TMI and DC (neutrophil migratory activity, NMA) (669.0+/-45.0 vs. 389.0+/-18.9). fMLP stimulated PMNs of RA patients showed defective migration compared to unstimulated samples as shown by (a) a reduced number of migrant PMNs (1799+/-93 PMN/mm2), (b) lower TMI (26.1+/-0.9%), (c) unremarkable altered distribution characteristic (22.9+/-0.8 mm) and (d) significant reduced migratory activity (600.0+/-30.0). Our data suggest that the high incidence of infections in RA patients may partly be caused by defective migratory activity of PMNs to bacterial chemoattractants as demonstrated by fMLP.

Adult↗
PubMed1998

Alcohol consumption and atherosclerosis: what is the relation? Prospective results from the Bruneck Study.

BACKGROUND AND PURPOSE: Potential effects of regular alcohol consumption on atherogenesis are still controversial mainly due to the lack of prospective population-based studies. METHODS: The Bruneck Study is a prospective population-based survey of atherosclerosis and its risk factors. The study population comprises a sex- and age-stratified random sample of men and women aged 40 to 79 years. Participation and follow-up were more than 90% complete. Changes in carotid atherosclerosis between the 1990 baseline and the first follow-up in 1995 were monitored by high-resolution duplex ultrasonography. Alcohol intake was quantified with a standardized questionnaire and prospective diet records. RESULTS: Alcohol consumption less than once a week (occasional drinking) had no effect on atherogenesis. The association between regular alcohol intake and incident carotid atherosclerosis (early atherogenesis) was J-shaped, with light drinkers facing a lower risk than either heavy drinkers or abstainers. Protection offered by alcohol consumption of <50 g/d appeared to act through inhibition of the injurious action of high levels of low-density lipoprotein (LDL) cholesterol. Excess risk of incident atherosclerosis observed among heavy alcohol consumers (> or =100 g/d) clearly surpassed the risk burden afforded by heavy smoking. The association between regular alcohol intake and incident carotid stenosis (advanced atherogenesis) was U-shaped. Odds ratios were generally shifted toward protection and did not rely on LDL cholesterol levels. We failed to find any differential effects of alcohol from various sources. All associations remained independently significant when we adjusted for lifestyle, coincidental smoking, and the metabolic complex associated with drinking. CONCLUSIONS: Our findings support the view that adverse and beneficial effects of alcohol on arterial disease are mediated in part by a dose-dependent promotion or deceleration of atherogenesis. The protection afforded by light drinking may possibly be attributed to antithrombotic effects and inhibition of the atherogenic action of high levels of LDL cholesterol.

Adult↗
PubMed1998

Prevalence of insulin resistance in metabolic disorders: the Bruneck Study.

The prevalence of insulin resistance in the most common metabolic disorders is still an undefined issue. We assessed the prevalence rates of insulin resistance in subjects with impaired glucose tolerance (IGT), NIDDM, dyslipidemia, hyperuricemia, and hypertension as identified within the frame of the Bruneck Study. The study comprised an age- and sex-stratified random sample of the general population (n = 888; aged 40-79 years). Insulin resistance was estimated by homeostasis model assessment (HOMA(IR)), preliminarily validated against a euglycemic-hyperinsulinemic clamp in 85 subjects. The lower limit of the top quintile of HOMA(IR) distribution (i.e., 2.77) in nonobese subjects with no metabolic disorders (n = 225) was chosen as the threshold for insulin resistance. The prevalence of insulin resistance was 65.9% in IGT subjects, 83.9% in NIDDM subjects, 53.5% in hypercholesterolemia subjects, 84.2% in hypertriglyceridemia subjects, 88.1% in subjects with low HDL cholesterol, 62.8% in hyperuricemia subjects, and 58.0% in hypertension subjects. The prevalence of insulin resistance in subjects with the combination of glucose intolerance (IGT or NIDDM), dyslipidemia (hypercholesterolemia and/or hypertriglyceridemia and/or low HDL cholesterol), hyperuricemia, and hypertension (n = 21) was 95.2%. In isolated hypercholesterolemia, hypertension, or hyperuricemia, prevalence rates of insulin resistance were not higher than that in nonobese normal subjects. An appreciable number of subjects (n = 85, 9.6% of the whole population) was insulin resistant but free of IGT, NIDDM, dyslipidemia, hyperuricemia, and hypertension. These results from a population-based study documented that 1) in hypertriglyceridemia and a low HDL cholesterol state, insulin resistance is as common as in NIDDM, whereas it is less frequent in hypercholesterolemia, hyperuricemia, and hypertension; 2) the vast majority of subjects with multiple metabolic disorders are insulin resistant; 3) in isolated hypercholesterolemia, hyperuricemia, or hypertension, insulin resistance is not more frequent than can be expected by chance alone; and 4) in the general population, insulin resistance can be found even in the absence of any major metabolic disorders.

Adult↗
PubMed1998

U-shaped and J-shaped relationships between serum insulin and coronary heart disease in the general population. The Bruneck Study.

OBJECTIVE: To evaluate the relationship existing between serum insulin and coronary heart disease (CHD) in the general population. RESEARCH DESIGN AND METHODS: In a cross-sectional survey on atherosclerosis and its risk factors, 500 men and 500 women aged 40-79 years were randomly selected from the population of Bruneck, Italy. Clinical, biochemical, and behavioral risk factors of atherosclerosis were assessed in the 936 subjects who participated in the study. Serum insulin was measured at fasting (n = 888) and 2 h (n = 811, known diabetic subjects were excluded) after an oral glucose load. CHD was ascertained by an abnormal electrocardiogram and/or a history of angina or myocardial infarction. RESULTS: Subjects were stratified according to serum insulin quintiles at fasting or 2 h after glucose loading. After adjustment for sex, age, BMI, smoking, physical activity, alcohol intake, and socioeconomic status (analysis of covariance), cardiovascular risk factors clustered in subjects of the top insulin quintile. Multiple logistic regression analysis, including sex and age in model 1, sex, age, BMI, glucose tolerance, socioeconomic status, and behavioral variables in model 2, or this set of variables together with triglycerides and apoproteins A1 and B, fibrinogen, and blood pressure status in model 3, revealed a significant association between high serum insulin and CHD when median insulin quintile was used as the reference class. Moreover, low serum insulin levels, such as those found in subjects of the lowest quintile, were independently related to CHD. These results were found either before (model 1) or after (models 2 and 3) adjusting for several covariates. Consistent results were found in men and women, as well as in younger and older subjects. CONCLUSIONS: Results of the present study suggest that both hyperinsulinemia and "hypoinsulinemia" are independent indicators of CHD. Furthermore, it is proposed that the relationship between CHD and fasting insulin is U-shaped, whereas that between CHD and postglucose insulin may be J-shaped.

Adult↗
PubMed1997

Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study.

BACKGROUND: Fe2+ released from tissue iron stores may accelerate lipid peroxidation by virtue of its pro-oxidant properties and thus promote early atherogenesis. METHODS AND RESULTS: The present prospective survey addresses the potential association between serum ferritin concentrations and the 5-year progression of carotid atherosclerosis as assessed by ultrasonographic follow-up evaluations. The study population comprises a random sample of 826 men and women 40 to 79 years old. Serum ferritin was one of the strongest risk predictors of overall progression of atherosclerosis. The main part of this association appeared to act through modification of the atherogenic potential of LDL cholesterol (OR [95% CI] for a 1-SD unit increase in ferritin at LDL levels of 2.5, 3.6, and 4.9 mmol/L: 1.55 [1.30 to 1.85], 1.77 [1.40 to 2.24], and 2.05 [1.50 to 2.80]; P=.0012 for effect modification). Changes in iron stores during the follow-up period modified atherosclerosis risk, in that a lowering was beneficial and further iron accumulation exerted unfavorable effects. All these findings applied equally to incident atherosclerosis and the extension of preexisting atherosclerotic lesions. The significance of prominent iron stores in the development of carotid stenosis was clearly less pronounced. Finally, ferritin and LDL cholesterol showed a synergistic association with incident cardiovascular disease and death (n=59). CONCLUSIONS: The present study provided strong epidemiological evidence for a role of iron stores in early atherogenesis and suggests promotion of lipid peroxidation as the main underlying pathomechanism. This hypothesis could in part explain the sex difference in atherosclerotic vascular disease.

Adult↗