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Biomedical subjects

Karin Schenck-Gustafsson

Publications and source records attributed to Karin Schenck-Gustafsson.

At least 19 recordsLinked to original sources

Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology.

Cardiovascular diseases (CVD) are the leading cause of mortality both in men and women. In Europe, about 55% of all females' deaths are caused by CVD, especially coronary heart disease and stroke. Unfortunately, however, the risk of heart disease in women is underestimated because of the perception that women are 'protected' against ischaemic heart disease. What is not fully understood is that women during the fertile age have a lower risk of cardiac events, but this protection fades after menopause thus leaving women with untreated risk factors vulnerable to develop myocardial infarction, heart failure, and sudden cardiac death. Furthermore, clinical manifestations of ischaemic heart disease in women may be different from those commonly observed in males and this factor may account for under-recognition of the disease. The European Society of Cardiology has recently initiated an extensive 'Women at heart' program to coordinate research and educational initiatives on CVD in women. A Policy Conference on CVD in Women was one of the first steps in the development of this program. The objective of the conference was to collect the opinion of experts in the field coming from the European Society of Cardiology member countries to: (1) summarize the state-of-the-art from an European perspective; (2) to identify the scientific gaps on CVD in women; and (3) to delineate the strategies for changing the misperception of CVD in women, improving risk stratification, diagnosis, and therapy from a gender perspective and increasing women representation in clinical trials. The Policy Conference has provided the opportunity to review and comment on the current status of knowledge on CVD in women and to prioritize the actions needed to advance this area of knowledge in cardiology. In the preparation of this document we intend to provide the medical community and the stakeholders of this field with an overview of the more critical aspects that have emerged during the discussion. We also propose some immediate actions that should be undertaken with the hope that synergic activities will be implemented at European level with the support of national health care authorities.

Age Distribution↗

Endothelial function in post-menopausal former elite athletes.

OBJECTIVE: To characterize endothelial function in postmenopausal former elite athletes in comparison to sedentary controls and to study the influence of hormone replacement therapy (HRT) on endothelial function in these groups of women. DESIGN: Cross-sectional study. SETTING: Research unit at a university hospital. PARTICIPANTS: Twenty postmenopausal former elite but still active endurance female athletes and 19 age-matched sedentary controls. The group of athletes and control subjects were each subdivided into two groups on the basis of utilization or non-utilization of HRT involving estrogen and gestagen. METHODS: Flow-mediated vasodilatation (FMD) was employed as an indicator of endothelial function. Fasting blood samples were analyzed for lipids and body composition determined by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURES: FMD, blood lipids and body composition. RESULTS: Former elite athletes not utilizing HRT demonstrated the highest FMD of all four subgroups, their values being significantly higher than those of control subjects not utilizing HRT (P < 0.05), whereas this difference was not seen between the subgroups of athletes and control subjects using HRT. Serum levels of cholesterol and low-density lipoprotein (LDL) and the percentage of fat mass were significantly lower in the former elite athletes than in the control group (P < 0.05 in all cases). However, these variables were not related to FMD. CONCLUSION: This investigation documents enhanced endothelial function in postmenopausal former elite endurance athletes not utilizing HRT, whereas the use of HRT equalizes FMD in former athletes and sedentary control subjects. Our findings suggest that long-term strenuous exercise has beneficial effects on endothelial function in postmenopausal women but that no further improvement can be obtained with HRT.

Case-Control Studies↗

Oral contraceptives improve endothelial function in amenorrheic athletes.

Athletic amenorrhea has been associated with endothelial dysfunction and unfavorable lipid profile. Estrogen substitution may reverse these metabolic consequences. The aim of this study was to evaluate the effects of oral contraceptives (OCs) on endothelial function measured as flow-mediated dilatation (FMD) of the brachial artery, the lipid profile, and blood markers of endothelial activation (inflammation) in amenorrheic athletes. Age- and body mass index-matched groups of young endurance athletes with amenorrhea (n = 11), regularly cycling athletes (n = 13), and sedentary controls (n = 12) were examined before and after 9 months of treatment with a low dose, monophasic, combined OC (30 mug ethinyl estradiol and 150 mug levonorgestrel). The amenorrheic athletes displayed the lowest FMD at baseline and the largest increase after OC treatment. FMD also increased in the control group, but not in the regularly menstruating athletes, who had the highest values of FMD before treatment. All three groups, particularly the controls, showed moderate unfavorable changes in the lipid profile in accordance with previous known effects of a second generation OC. Furthermore, there was an overall increase in some inflammatory markers (high sensitive C-reactive protein and TNF-alpha) and a decrease in one of the markers (vascular cell adhesion molecule-1). We conclude that amenorrheic athletes benefit from treatment with OC with respect to endothelial function. OC treatment is also associated with some modest alterations in the lipid profile and in markers of inflammation.

Adolescent↗

Does body mass index, smoking, lipoprotein levels, surgically induced menopause, hormone replacement therapy, years since menopause, or age affect hemostasis in postmenopausal women?

BACKGROUND: Controversy still exists as to the relative importance of menopausal status and lifestyle factors for the risk of coronary heart disease in women. OBJECTIVE: The purpose of this study was to assess the influence of body mass index (BMI), smoking,lipoprotein levels, surgically induced menopause, hormone replacement therapy (HRT), years since menopause, and age on hemostasis in apparently healthy postmenopausal women. METHODS: Lipoproteins (total cholesterol [TC], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides [TG]), and hemostatic factors (fibrinogen, von Willebrand factor antigen [vWFag], coagulation factors VIIag [FVIlag] and VIIa [FVIIa], plasminogen activator inhibitor 1 [PAI-1]) were each measured once. A forward, stepwise, multiple regression analysis was used to assess variations in hemostatic parameters. RESULTS: A group of 292 healthy Stockholm women recruited from the census register participated in the Stockholm Female Coronary Risk Study as controls. Of these women, 260 participated in the present study. BMI, smoking, lipoprotein levels, surgically induced menopause, and years since menopause (1-5 y) were found to be associated with a 31% increase in fibrinogen levels. A 7% increase in FVIIa levels was attributed to TC, BMI, and HRT. Years since menopause (1-15 y), TG, TC, BMI, and HRT were associated with an increase of up to 26% in FVIIag levels. A 9% increase in vWFag correlated with HDL-C and years since menopause (1-10, 11-14, and > or =15 y). BMI and TG explained a 21% and 3% increase, respectively, in PAI-1 levels. Neither the use of HRT nor years since menopause had any influence on hemostasis. CONCLUSION: BMI, high levels of TC and TG, and low HDL-C levels appear to be more important than hormonal status in their impact on hemostatic variables in healthy postmenopausal women.

Adult↗

Athlete's heart in postmenopausal former elite endurance female athletes.

OBJECTIVE: To investigate cardiac structure and function and exercise capacity in senior former elite athlete women. DESIGN: Cross-sectional study. PARTICIPANTS: Twenty postmenopausal former elite endurance athletes and 19 age-matched sedentary controls. METHODS: All subjects underwent transthoracic Doppler echocardiography and maximal exercise test on a bicycle ergometer. MAIN OUTCOME MEASURES: Cardiac chamber dimensions, wall thickness, cardiac function, and exercise capacity. RESULTS: The athletes had a greater exercise capacity (183 +/- 26 vs. 144 +/- 36 W; P < 0.01) compared with controls. Three of 20 (15%) athletes and 9 of 19 (47%) controls exhibited ST depressions during exercise test (P < 0.05). Echocardiographic measurements demonstrated larger left ventricular diameter (2.9 +/- 0.3 vs. 2.6 +/- 0.2 cm/m; P < 0.01), left ventricular volume (64 +/- 14 vs. 54 +/- 8 mL/m; P < 0.05), right ventricular diameter (1.6 +/- 0.2 vs. 1.4 +/- 0.2 cm/m; P < 0.01), left atrial volume (20.8 +/- 6 vs. 16.6 +/- 3.6 mL/m; P < 0.05), and stroke volume (45 +/- 10 vs. 36 +/- 5 mL/m; P < 0.01) in athletes than controls, whereas interventricular septum (9.3 +/- 1.7 vs. 10.1 +/- 1.8 mm; P > 0.05) and posterior wall thickness (9.0 +/- 1.6 vs. 9.2 +/- 1.0 mm; P > 0.05) did not differ between the groups. CONCLUSIONS: This study demonstrates cardiac enlargement without increased wall thickness in postmenopausal former elite endurance athlete women. Our results also indicate that long-term training maintains a high level of cardiovascular fitness in the aging female athletes.

Cardiac Output↗

Influence of factor VII gene polymorphisms and environmental factors on plasma coagulation factor VII concentrations in middle-aged women with and without manifest coronary heart disease.

Plasma concentrations of coagulation factorVII (FVII) are determined by environmental and genetic factors. The influence of functional polymorphisms in the FVII gene (-670A>C, -402G>A, -401G>T and R353Q) and of established cardiovascular risk factors on plasma concentrations of FVII were investigated in a representative sample of middle-aged women with (n=238) and without (n=220) coronary heart disease (CHD). Specific and sensitive assays were used to measure FVII antigen (VIIag) and activated factorVII (VIIa). The effect of genotypes was markedly stronger on VIIa than on VIIag, with the percentage variation in FVII levels accounted for by genotypes being greater in controls than in patients. Of the four polymorphisms examined, only the R353Q contributed to the variation inVIIa (24.1% in patients and 30.3% in controls). The -401G>T and -670A>C promoter polymorphisms together accounted for 12.2% of the variation in VIIag amongst patients whereas the -401G>T polymorphism alone contributed 19.7% of the variation in VIIag in controls. Serum triglycerides exerted a major influence onVIIag in both patients (13.0%) and controls (7.2%). Three main haplotypes emerged from the four polymorphisms which accounted for 98% of all haplotypes. Large-scale prospective studies of CHD including FVII haplotypes and sensitive and specific FVII measurements are needed in women.

Analysis of Variance↗

Amenorrhea in female athletes is associated with endothelial dysfunction and unfavorable lipid profile.

The aim of this study was to evaluate endothelial function measured as flow-mediated dilatation (FMD) of the brachial artery and blood markers of cardiovascular disease in young female endurance athletes with menstrual disturbance. Age- and body mass index-matched groups of young endurance athletes with amenorrhea (n = 14), oligomenorrhea (n = 9), and regular cycles (n = 12) and sedentary controls (n = 12) were compared with respect to endothelial function, lipid profile, markers of inflammation, and endocrine status. We found a significantly decreased FMD in the amenorrheic athletes, compared with all other groups. Amenorrheic athletes also had the most unfavorable lipid profile with significantly higher total cholesterol and low-density lipoprotein, compared with the other athlete groups. The oligomenorrheic athletes had the lowest levels of total cholesterol, low-density lipoprotein, and apolipoprotein B of all groups and significantly lower in comparison with the amenorrheic group. However, with respect to FMD, the oligomenorrheic group represented an intermediate between amenorrheic and regularly cycling subjects. There was a gradual impairment of FMD and the lipid profile to the degree of menstrual disturbance supporting an association with estrogen status. We conclude that amenorrhea in young endurance athletes is associated with endothelial dysfunction and unfavorable lipid profile. Additional studies are needed to elucidate the clinical implications of these results with regard to long-term risk for cardiovascular disease.

Adolescent↗

Alcohol consumption and coronary atherosclerosis progression--the Stockholm Female Coronary Risk Angiographic Study.

OBJECTIVE: To assess the association of alcohol intake with progression of coronary atherosclerosis. Although moderate drinkers have a lower risk of coronary heart disease than abstainers, the relation of alcohol use and coronary atherosclerosis has not been well studied. METHODS AND RESULTS: In the Stockholm Female Coronary Risk Angiographic Study, we evaluated 103 women, aged 65 years or younger, hospitalized with acute myocardial infarction or unstable angina pectoris who underwent serial quantitative coronary angiography 3-6 months following their index event and repeated an average of 3 years and 3 months (range 2-5 years) later. Individual alcoholic beverage consumption was assessed by a standardized questionnaire. We used mixed model analysis to estimate the effect of alcohol consumption on progression of coronary atherosclerosis, as measured by mean luminal diameter change, controlling for age, smoking, body-mass index, education, physical activity, index cardiac event, menopausal status, diabetes, and history of dyslipidemia. Of the 93 women with complete information on alcohol intake, 14 consumed no alcohol (abstainers), 55 consumed up to 5 g of alcohol per day (light drinkers), and 24 consumed more than 5 g of alcohol per day (moderate drinkers). Coronary atherosclerosis progressed by a multivariate-adjusted average of 0.138 mm (95% confidence interval (CI): 0.027-0.249) among abstainers, 0.137 mm (95% CI: 0.057-0.217) among light drinkers, and -0.054 mm (95% CI: -0.154 to 0.047) among moderate drinkers (P < 0.001). The inverse association persisted in analyses stratified by index event. No beverage type appeared to confer particular benefit. CONCLUSIONS: Among middle-aged women with coronary heart disease, moderate alcohol consumption (over 5 g/day) was protective of coronary atherosclerosis progression.

Adult↗

Decreased levels of von Willebrand factor-cleaving protease in coronary heart disease and thrombotic thrombocytopenic purpura: study of a simplified method for assaying the enzyme activity based on ristocetin-induced platelet aggregation.

The haemostatic activity of von Willebrand Factor (VWF) is dependent on VWF multimer stability. Fragments, arising from the proteolytic cleavage of the multimers by VWF-cleaving protease, are ineffective in initiating platelet aggregation. We designed a simple method to determine the protease activity, which was expressed as the reduction in the level of ristocetin-induced platelet aggregation between the inactive enzyme and the enzyme when activated by the addition of calcium. Samples from senior women (n = 14) with chronic coronary heart disease (CHD), age-matched control subjects (n = 15) and young healthy individuals (n = 13), as well as patients with either thrombotic thrombocytopenic purpura (TTP) (n = 2) or von Willebrand disease type 2A (VWD-2A) (n = 2), were examined. The lower protease activity observed in the CHD group, compared with the control subjects, indicated that the increased levels of VWF found in CHD relate to impaired enzyme function. The assessment of TTP patients reconfirmed the reduced protease activity previously observed in this disorder. In VWD-2A, normal enzyme function was observed, suggesting that there is an increased sensitivity of the mutated VWF protein to the protease, rather than an increase in the activity or quantity of the enzyme involved in pathogenesis. In summary, the present simplified method efficiently determines VWF protease activity and is suitable for use in laboratories where platelet aggregation analyses can be performed.

ADAM Proteins↗

Vital exhaustion in relation to lifestyle and lipid profile in healthy women.

"Vital exhaustion," characterized by fatigue, irritability, and demoralization, precedes new and recurrent coronary events. Biological mechanisms explaining this association are not fully understood. The objective was to investigate the relationship between vital exhaustion, lifestyle, and lipid profile. Vital exhaustion, smoking, body mass index (BMI), alcohol consumption, exercise capacity, and serum lipids were determined in 300 healthy women, aged 56.4 +/- 7.1 years. No statistically significant associations were found between vital exhaustion and lifestyle variables. Divided into quartiles, vital exhaustion was inversely related to high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 in a linear fashion after adjustment for age, BMI, exercise capacity, and alcohol consumption. A multivariate-adjusted vital exhaustion-score in the top quartile, as compared to one in the lowest, was associated with 12% lower HDL-C and 8% lower apolipoprotein A1 (p < .05). In conclusion, alterations in lipid metabolism may be a possible mediating mechanism between vital exhaustion and coronary heart disease. The impact of lifestyle variables was weak.

Alcohol Drinking↗

Repolarization measures and their relation to sex hormones in postmenopausal women with cardiovascular disease receiving hormone replacement therapy.

Women are more susceptible to the development of Torsades de Pointes ventricular tachycardia and have a longer heart rate-corrected QT interval than men. A causal role for estrogen has been implicated. The purpose of this study was to investigate if hormone replacement therapy (HRT) resulted in any changes in noninvasive depolarization and repolarization measurements, and to study their relation to circulating concentrations of sex hormones. Sixty postmenopausal women with cardiovascular disease (mean age 59 +/- 7 years; range 44 to 75) were randomized to receive oral conjugated estrogens, transdermal estradiol-17-beta (both with addition of progestins), or placebo. QRS, QT, and JT intervals and their dispersion on 12-lead electrocardiograms were analyzed at baseline, and after 6 and 12 treatment cycles of HRT. Blood samples for analyses of serum concentration of estrogens and androgens were obtained on the same occasions. Neither mean RR, QT, QTc, JT, and JTc intervals, nor QT and JT dispersion changed during treatment. There was a significant inverse relation between the mean JTc interval and the serum concentration of estradiol-17-beta, independent of age, testosterone levels, and abdominal obesity. There was also a significant inverse relation between the change in androstenedione levels and the change in QT interval (Spearman -0.35, p = 0.028) or JT interval (Spearman -0.41, p = 0.009) at 6 treatment cycles compared with baseline. In conclusion, treatment with oral conjugated estrogens or transdermal estradiol-17-beta combined with progestins did not alter depolarization or repolarization measurements. However, the inverse relation between repolarization and androgens fits with an effect of androgens on repolarization in postmenopausal women.

Administration, Cutaneous↗