Sex differences in the presentation of stroke.

Stroke affects both men and women of all ages, although the condition is more common among the elderly. Stroke occurs at an older age among women than among men; although the incidence is lower among women than among men, as women have a longer life expectancy their lifetime risk is slightly higher. Ischemic stroke is the most common type of stroke; and reperfusion treatment is possible if the patient reaches hospital early enough. Thrombolysis and thrombectomy are time-sensitive treatments - the earlier they are initiated the better is the chance of a positive outcome. It is therefore important to identify a stroke as soon as possible. Medical personnel can readily identify typical stroke symptoms but the presentation of non-traditional stroke symptoms, such as impaired consciousness and altered mental status, is often associated with a significant delay in the identification of stroke and thus delay in or inability to provide treatment. Non-traditional stroke symptoms are reported to be more common in women, who are thereby at risk of delayed recognition of stroke and treatment delay.

Type 2 diabetes and cardiovascular disease in women.

Cardiovascular disease is the leading cause of death in both men and women. This is also true for patients with diabetes. In general, differences between the sexes are present in several areas, such as epidemiology, pathophysiology, diagnostics, treatment response and prognosis, as well as the way in which disease is experienced and expressed. Cardiovascular disease presents later in life in women, who are therefore more likely to suffer from comorbidities. However, this age-related difference is attenuated in women with diabetes, who suffer their first myocardial infarction at about the same age as men with diabetes. Diabetes mellitus increases the risk of cardiovascular disease by three to four times in women and two to three times in men, after adjusting for other risk factors. This paper describes the differences in cardiovascular disease in men and women and the special situation of women with type 2 diabetes when it comes to risk factors, symptoms and the setting of acute coronary syndromes. Furthermore, it highlights the importance of sex-specific analyses in clinical research to improve our knowledge of cardiovascular disease in women in general and in women with diabetes in particular. The importance of taking sex into account when treating women and men at risk of cardiovascular disease is discussed.

Psychosocial stress and atherosclerosis: family and work stress accelerate progression of coronary disease in women. The Stockholm Female Coronary Angiography Study.

OBJECTIVE: To examine the impact of psychosocial stress, experienced in the family and work life, on the progression of coronary atherosclerosis in women cardiac patients. DESIGN: Longitudinal follow-up study. The mean luminal diameter change over 3 years was averaged over 10 predefined coronary segments, representing the entire coronary tree. Stress in family life was measured by using the Stockholm Marital Stress Scale and that of work life by the demand-control questionnaire. SUBJECTS: Amongst patients enrolled in the Stockholm Female Coronary Angiography Study, 80 women were evaluated for stress exposure and coronary atherosclerosis progression using serial quantitative coronary angiography. RESULTS: Multi-variable-controlled mixed models anova analyses revealed that women with high stress from either family or work had significant disease progression over 3 years, whereas those with low stress had only slight progression. In women who were free of stress from either family or work life, i.e. they were satisfied with both of these life domains, the coronary artery changes had regressed. Their mean coronary luminal diameter increased by 0.22 mm (95% CI: 0.10; 0.35 mm) when compared with women who experienced stress from both sources, whose luminal diameter decreased by 0.20 mm (95% CI: -0.14; -0.25). These associations were independent of baseline luminal diameter and standard cardiovascular risk factors, including age smoking, hypertension and HDL at baseline. CONCLUSIONS: Stress from family or work life may accelerate coronary disease processes in women, whereas relative protection may be obtained from a satisfactory job and a happy marriage.

Physical activity and exercise performance predict long-term prognosis in middle-aged women surviving acute coronary syndrome.

AIM: To evaluate the importance of exercise testing (ET) parameters and leisure time physical activity in predicting long-term prognosis in middle-aged women hospitalized for acute coronary syndrome (ACS). METHODS AND RESULTS: Women aged <66 years recently hospitalized for ACS in the Greater Stockholm area in Sweden were recruited. All underwent baseline clinical examinations including ET and then were followed up for 9 years. Nonparticipation in ET had a hazard ratio of 4.26 (95% confidence interval 2.02-8.95) for total mortality and 3.03 (1.03-8.91) for cardiovascular mortality. All ET parameters were significantly different between survivors than nonsurvivors, except for chest pain and ST-segment depression during ET. Sedentary lifestyle and ET parameters were related to total mortality and cardiovascular mortality in a multivariate analysis adjusting for potential confounders. Predictors of total mortality were sedentary lifestyle 2.94 (1.31-6.62), exercise time 1.75 (1.07-2.87) and inadequate haemodynamic responses: low increase in pulse rate 2.04 (1.16-3.60) and systolic blood pressure (SBP) 1.88 (1.19-2.95) from rest to peak exercise. Parameters that predicted cardiovascular mortality were sedentary lifestyle 3.15 (1.13-8.74) and poor increase in SBP 2.76 (1.30-5.86) from rest to peak exercise. The relation of sedentary lifestyle to survival was substantially weakened when exercise parameters were added to the multivariate analysis model. CONCLUSION: In female patients <66 years surviving ACS, important independent predictors of long-term all-cause mortality were sedentary lifestyle, low physical fitness and inadequate pulse rate and SBP increase during exercise. Predictors of cardiovascular mortality were sedentary lifestyle and inadequate blood pressure response during exercise.

Circulating concentrations of hemostatic factors and two "steroid sensitive proteins" during oral hormone replacement therapy in women with coronary heart disease.

OBJECTIVE: To study a possible use of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) as markers for changes in hemostatic factors during oral postmenopausal hormone replacement therapy (HRT). METHODS: Twenty-eight postmenopausal women were treated with oral conjugated equine estrogens+oral medroxyprogesterone acetate (CEE + MPA, n = 15) or with placebo (n = 13). Serum SHBG, CBG, testosterone, cortisol and plasma coagulation factors, coagulation inhibitors and markers of coagulation activation were measured before and after 6 and 12 months of treatment. RESULTS: Pretreatment plasminogen activator inhibitor 1 (PAI-1) levels correlated negatively to SHBG and antithrombin III (AT III) negatively to total and free cortisol. In the CEE + MPA group, CBG, SHBG and Factor VII increased, and PAI-1, AT III and free testosterone decreased during treatment. No significant changes were found in plasma von Willebrand factor antigen, thrombin-antithrombin complex, fibrin D-dimer and fibrinogen. A significant, negative correlation was found between changes in SHBG and PAI-1. No changes were found in the placebo group. CONCLUSION: The only correlation found between changes in "steroid sensitive" proteins and hemostatic factors was between increased SHBG and a possibly beneficial effect of estrogens, i.e. decreased PAI-1 values. SHBG or CBG could not be used as predictors of increased cardiovascular risk during postmenopausal oral HRT.

Heart rate variability in long-term risk assessment in middle-aged women with coronary heart disease: The Stockholm Female Coronary Risk Study.

OBJECTIVES: Low heart rate variability (HRV) is associated with poor prognosis after acute coronary events in men. In women, the prognostic impact is not well documented. The objective of this study was to assess the long-term predictive power of HRV on mortality amongst middle-aged women with coronary heart disease (CHD). DESIGN, SETTINGS AND SUBJECTS: Consecutive women below 65 years hospitalized for an acute coronary syndrome during a 3-year period in Stockholm were examined for cardiovascular prognostic factors including HRV, and followed for a median of 9 years. An ambulatory 24-h electrocardiograph was recorded during normal activities, 3-6 months after hospitalization. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high-frequency (HF) power, low-frequency (LF) power, very-low frequency (VLF) power and LF/HF ratio. Using Cox proportional hazards regression, the hazard ratios (HR) for each 25% decrease of the HRV parameters were assessed. RESULTS: After controlling for the independent, significant predictors of mortality amongst the clinical variables, the following HRV parameters were found to be significant predictors of all-cause mortality: SDNN index [HR 1.56, 95% confidence intervals (CI) 1.19-2.05], total power (HR 1.21, 95% CI 1.08-1.35), VLF power (HR 1.22, 95% CI 1.09-1.36), LF power (HR 1.18 95%, CI 1.07-1.30) and HF power (HR 1.18, 95% CI 1.05-1.33). The results were essentially the same when cardiovascular mortality was used as end-points. The HRV parameters were stronger predictors of mortality in the first 5 years following the index event. CONCLUSION: Low HRV is a predictor of long-term mortality amongst middle-aged women with CHD when measured 3-6 months after hospitalization for an acute coronary syndrome, even after controlling for established clinical prognostic markers.

A common polymorphism in the fatty acid transport protein-1 gene associated with elevated post-prandial lipaemia and alterations in LDL particle size distribution.

The fatty acid transport proteins (FATPs) have been implicated in facilitated cellular uptake of non-esterified fatty acids (NEFAs), thus having the potential to regulate local and systemic NEFA concentrations and metabolism. Hypothesising that genetic variation within the FATP genes may affect lipid metabolism, we investigated a G/A substitution at position 48 in intron 8 of the fatty acid transport-1 (FATP1) gene with respect to associations with fasting and post-prandial plasma lipid and lipoprotein variables in 628 healthy 50-year-old Swedish men and 426 Swedish women, aged 37-65 years. A subset of 105 men with the apoE3/E3 genotype underwent an oral fat tolerance test. Although fasting plasma TG concentrations were not different, male A/A individuals had significantly higher post-prandial TG concentrations and VLDL(1) (S(f) 60-400 apoB100)-to-VLDL(2) (S(f) 20-60 apoB100) ratio compared to male G/A and G/G individuals. A/A individuals apparently failed to suppress plasma NEFA concentrations during the oral fat tolerance test. Furthermore, fasting plasma concentrations of the largest, most buoyant LDL subfraction (LDL-I) were significantly lower in carriers of the A allele in the male cohort. Electromobility shift assays and reporter gene studies indicated that binding of nuclear factors and effect on transcriptional activity differ between the intron 8 alleles. These findings suggest that through regulation of NEFA trafficking, FATP1 might play a role in post-prandial lipid metabolism and development of cardiovascular disease.

Significant predictors of poor prognosis in women aged

OBJECTIVES: The aim of this study was to evaluate the importance of different clinical parameters predicting long-term cardiac prognosis in younger women with an acute coronary event. DESIGN: The Stockholm Female Coronary Risk Study is a follow-up study in women 2.0 mmol L-1 (HR 2.46, 95% CI 1.06-5.54). AMI as index event and diabetes mellitus were the most significant predictors in a multivariate statistical model. Diabetes mellitus was the strongest predictor when the analysis was repeated in the total patient cohort, integrating patients that did not participate in the extended investigations. CONCLUSION: Women aged

Cardiovascular reactivity to mental stress in the Stockholm Female Coronary Risk Study.

OBJECTIVE: This study evaluated the ability of mental stress testing to discriminate between women with and without CHD, and among women with different disease manifestations, taking into account history of hypertension and beta-blocker use. METHODS: Analyses were based on data from a community-based case-control study of women aged 65 years or younger. The study group consisted of 292 women who were hospitalized for an acute event of CHD, either AMI or unstable AP in Stockholm between 1991 and 1994. Controls were matched to cases by age and catchment area. Cardiovascular reactivity and emotional response to an anagram task solved under time pressure were measured 3 to 6 months after hospitalization. RESULTS: Patients reacted with smaller increases in heart rate (4 bpm) than their controls (7 bpm). Results for the rate-pressure product were similar. Cardiovascular reactions did not distinguish patients with AP from those with AMI. History of hypertension (present in 50% of patients and 11% of controls) was related to enhanced diastolic blood pressure reactivity. Patients on beta-blockers (66%) had lower heart-rate levels throughout testing, but did not differ in their cardiovascular stress reactions when compared with the remaining participants. CONCLUSIONS: Women with heart disease have somewhat lower heart-rate responses to stress than healthy age-matched controls. History of hypertension is related to enhanced diastolic blood pressure reactivity to mental stress in both patients and controls.

Are increased levels of von Willebrand factor in chronic coronary heart disease caused by decrease in von Willebrand factor cleaving protease activity? A study by an immunoassay with antibody against intact bond 842Tyr-843Met of the von Willebrand factor protein.

Low levels of von Willebrand factor (VWF) in von Willebrand's disease type 2A (VWD 2A) result from increased cleavage of the bond 842Tyr-843Met in the VWF protein by VWF cleaving protease. On the other hand, decreased levels of this protease result in unusually large VWF in thrombotic thrombcytopenic purpura with thrombotic complications. In the present study, we designed an enzyme-liked immunosorbent assay of VWF cleaving protease activity to be used to assess whether the high levels of VWF in coronary heart disease (CHD) relate to a deficiency of this protease. Plasma samples with added Pefabloc and CaCl(2) were incubated with purified VWF coated on a microtiter plate. The remaining undigested multimers were quantified by an antibody directed against the intact 842Tyr-843Met bond of the VWF protein. Phosphate-buffered saline (PBS), instead of plasma, was used to obtain the initial level of coated undigested VWF. The reduction in absorbance at 492 nm between PBS and the unknown sample was taken as a measure of the protease activity. The assay was applied to plasma samples from 21 senior women with chronic CHD (cases) and 34 age-matched controls, as well as to samples from three patients with VWD 2A. The protease activity was similar in the two women groups (P>.05), although the VWF antigen levels were higher in the cases (P<.01). The VWD 2A patients had similar plasma levels of the protease to that in normal pooled plasma (NPP). In the senior controls, the protease activity correlated with the subject age (r's=-.61, P<.01, n=34). In conclusion, the developed method is specific for evaluating the protease function on VWF cleavage. The moderate increase of VWF antigen in chronic CHD may not depend on the protease activity. The age influence on the protease levels supports earlier findings of higher VWF levels in healthy older subjects. A high sensitivity of the mutated protein of VWF for the protease effect rather than increases in activity or quantity of the enzyme is probably involved in the pathogenesis of VWD 2A.

[Management of cardiovascular diseases is characterized by male perspective. Women are subjected to incorrect management, diagnosis and treatment]. / Hantering av hjärt--kärlsjukdom präglas av manligt perspektiv. Kvinnor får felaktiga omhändertaganden, diagnoser och behandlingar.

In women as well as in men cardiovascular disease is common, and almost as many women as men suffer from myocardial infarction every year in Sweden. In spite of this, studies on female cardiovascular disease are few in number. Knowledge about differences in risk factors, prevention, treatment and management is not common. Female cardiovascular disease starts approximately ten years later than in men and consequently most women are excluded from studies because of low age limits for inclusion. Primary preventive effects of e.g. acetylsalicylic acid, lipid-lowering drugs, vitamins and exercise have only been studied in healthy men, but the conclusions have been applied on women as well. The effects of reducing triglyceride levels or abdominal obesity in women--important risk factors for cardiovascular disease--have not been studied in controlled randomized studies. In women, angina is a non-specific symptom, and false positive ECG's are much more frequent than in men. The fact that a woman has to present as a man in order to be treated professionally (the Yentl syndrome) is still at hand. There is a great need for spreading current knowledge regarding gender differences among colleagues and medical students.

Coagulation factor VII in middle-aged women with and without coronary heart disease.

Epidemiological studies of coagulation factor VII as a risk factor for coronary heart disease (CHD), mainly conducted in men, have shown discrepant results. We examined the associations of coagulation factor VII antigen (VIIag) and activated factor VII (VIIa) with manifest CHD in a community-based case-control study of women aged < or =65 years. Mean plasma concentrations of VIIag and VIIa in patients and controls were 443 +/- 10(8) and 418 +/- 89 ng/L (p <0.01) and 5.26 +/- 2.21 and 4.90 +/- 1.65 ng/L (NS), respectively. The odds ratio (OR) for CHD for the highest versus the lowest quartile of VIIag was 1.75 (95% CI, 1.05 to 2.92). The adjusted OR was 0.76 (95% CI, 0.28-1.98) after controlling for other cardiovascular risk factors. The corresponding ORs for VIIa were non-significant. In conclusion, the plasma concentration of VIIa was not significantly increased in a large group of women with precocious CHD, and VIIag levels, although elevated, were not independently associated with manifest disease.

Marital stress worsens prognosis in women with coronary heart disease: The Stockholm Female Coronary Risk Study.

CONTEXT: Psychosocial stress has been associated with incidence of coronary heart disease (CHD) in men, but the prognostic impact of such stress rarely has been studied in women. OBJECTIVE: To investigate the prognostic impact of psychosocial work stress and marital stress among women with CHD. DESIGN AND SETTING: Population-based, prospective follow-up study conducted in the city of Stockholm, Sweden. PARTICIPANTS: A total of 292 consecutive female patients aged 30 to 65 years (n = 279 working or cohabiting with a male partner) who were hospitalized for acute myocardial infarction or unstable angina pectoris between February 1991 and February 1994. Patients were followed up from the date of clinical examination until August 1997 (median, 4.8 years). MAIN OUTCOME MEASURES: Recurrent coronary events, including cardiac death, acute myocardial infarction, and revascularization procedures, by marital stress (assessed using the Stockholm Marital Stress Scale, a structured interview) and by work stress (assessed using the ratio of work demand to work control). RESULTS: Among women who were married or cohabiting with a male partner (n = 187), marital stress was associated with a 2.9-fold (95% confidence interval [CI], 1.3-6. 5) increased risk of recurrent events after adjustment for age, estrogen status, education level, smoking, diagnosis at index event, diabetes mellitus, systolic blood pressure, smoking, triglyceride level, high-density lipoprotein cholesterol level, and left ventricular dysfunction. Among working women (n = 200), work stress did not significantly predict recurrent coronary events (hazard ratio, 1.6; 95% CI, 0.8-3.3). CONCLUSIONS: Our results indicate that marital stress but not work stress predicts poor prognosis in women aged 30 to 65 years with CHD. These findings differ from previous findings in men and suggest that specific preventive measures be tailored to the needs of women with CHD.

Intracoronary ultrasound measurements in women with myocardial infarction without significant coronary lesions.

METHODS: Morphologic characteristics of coronary arteries in eight women with myocardial infarction and angiographically normal or not significantly stenosed vessels were investigated with intracoronary ultrasound. The infarct-related vessel was assessed by three-dimensional volumetric analysis and compared with a control vessel from a noninfarcted area. RESULTS: Atherosclerosis was found in all infarct-related arteries. The plaques were predominantly soft, eccentric, poorly calcified, and with little lipid pools or none at all. Although the average area and thickness of plaques and cross-sectional narrowing of the infarct-related arteries were greater than those of control arteries, there were no pathognomonic characteristics of plaques in the infarct-related vessels. CONCLUSION: The possibility that atherosclerosis is the main etiologic factor for myocardial infarction can not be excluded even for women without an angiographically obvious coronary stenosis in the infarct-related vessels.

Depressive symptoms and lack of social integration in relation to prognosis of CHD in middle-aged women. The Stockholm Female Coronary Risk Study.

AIMS: Several studies have reported that women with coronary heart disease have a poorer prognosis than men. Psychosocial factors, including social isolation and depressive symptoms have been suggested as a possible cause. However, little is known about these factors and their independent predictive value in women. Therefore, we investigated the prognostic impact of depression, lack of social integration and their interaction in the Stockholm Female Coronary Risk Study. METHODS AND RESULTS: Two hundred and ninety-two women patients aged 30 to 65 years and admitted for an acute coronary event between 1991 and 1994, were followed for 5 years from baseline assessments, which were performed between 3 and 6 months after admission. Lack of social integration and depressive symptoms, assessed at baseline by standardized questionnaires, were associated with recurrent events, including cardiovascular mortality, acute myocardial infarction and revascularization procedures (percutaneous transluminal coronary angioplasty and coronary artery bypass grafting). Adjusting for age, diagnosis at index event, symptoms of heart failure, diabetes mellitus, high density lipoprotein (HDL) cholesterol, history of hypertension, systolic blood pressure, smoking, sedentary lifestyle, body mass index, and severity of angina pectoris symptoms, the hazard ratio associated with low (lowest quartile) as compared to high social integration (upper quartile) was 2.3 (95% CI 1.2-4.5) and the hazard ratio associated with two or more (upper three quartiles) as compared to one or no depressive symptoms was 1.9 (95% CI 1.02-3.6). CONCLUSIONS: The presence of two or more depressive symptoms and lack of social integration independently predicted recurrent cardiac events in women with coronary heart disease. Women who were free of both these risk factors, had the best prognosis.