Cerebrovascular Disease In Women Research Articles

CEREBROVASCULAR DISEASE AND PREGNANCY

Approximately 12%–27% of cerebrovascular disease in women of childbearing age is associated with pregnancy. The reported incidence of stroke in pregnancy ranges from 0.01%–0.05%. While these events are uncommon, they are often clinically devastating. The Center for Disease Control's (CDC) review of death certificates in all 50 states and the District of Columbia found that neurologic or neurovascular problems are one of the leading causes of mortality in pregnancy.

Changes in Cardiovascular Hospitalization and Comorbidity of Heart Failure in the United States: Findings from the National Hospital Discharge Surveys 1980–2006

Objective This study aimed to update the long-term trend of coronary heart disease (CHD), cerebrovascular disease (CBVD), and heart failure (HF) hospitalization rates and HF comorbidity among adults aged 65 and older in the United States. Methods Data from the National Hospital Discharge Surveys between 1980 and 2006 were used. CHD, CBVD, and HF were defined using the principal (first-listed) diagnosis of disease at hospital discharge according to the ICD-9-CM code. Census estimated population data (2000) were used to estimate age and gender-specific hospitalization rates. Results Age-adjusted CHD and CBVD hospitalization rates have significantly decreased between 1980 and 2006, with an estimated annual decrease rate of 2.24% for CHD and 1.55% for CBVD in men, and 2.36% for CHD and 1.34% for CBVD in women. However, the absolute numbers of CHD and CBVD hospitalization continued to increase partly because of the aging population. Furthermore, HF hospitalization rates have significantly increased with an estimated annual rate increase of 1.20% in men and 1.55% in women between 1980 and 2006. Of six selected co-morbidities, about 50% in men and 40% in women with HF had a coexisting disease of CHD, followed by chronic obstructive pulmonary disease, diabetes mellitus, renal failure, and pneumonia. Conclusions While the burden of CHD and CBVD remains the major public health problem, HF has emerged as a new challenge in cardiovascular disease control, characterized by increased trends of HF hospitalization and increased comorbidities from major diseases.

Impact of cardiovascular diseases on activity limitations and need for help among older persons.

The aim of this study was to estimate the importance of specific chronic cardiovascular diseases (CVDs) as determinants of disability. One thousand two hundred eighty-eight (86%) participants from a random population sample of 1,500 individuals (from two geographical regions of Finland) aged 65-74 years were interviewed and clinically examined in 1997. CVDs were strongly associated with disability. However, mental disorders were the strongest determinant of disability. Of specific CVDs, cerebrovascular diseases in men, and myocardial infarction, heart failure, and cerebrovascular diseases in women were significantly associated with disability after adjustment for age and comorbidity. In men 33% and in women 24% of disability was attributable to CVD, excluding lone hypertension. CVDs are important determinants of disability among Finns aged 65-74 years. Due to the growing number of elderly people with CVDs, disability associated with these diseases is likely to become a growing social and health burden to the community.

Editorial Comment—Female Sex: A Questionable Risk Factor for Carotid Endarterectomy

The misconception that clinical manifestations of cardiovascular disease are a much more significant problem among male patients is hard to eliminate, supported by the higher incidence of cardiac, cerebrovascular, and peripheral arterial diseases in men than in women.1 Our understanding of cerebrovascular disease in women is hampered by a paucity of studies including an adequate number of female patients. Most studies are heavily biased toward the male sex. The efficacy of aspirin in primary and secondary stroke prevention trials has been demonstrated almost exclusively in men.2 Men were also the majority of the population recruited in the major clinical trials on symptomatic (North American Symptomatic Carotid Endarterectomy Trial [NASCET] and European Carotid Surgery Trial [ECST])3,4 and asymptomatic (Asymptomatic Carotid Atherosclerosis Study [ACAS]) carotid stenoses,5 and no women were enrolled in the Veteran Administration trials.6,7 Unfortunately, neither the original report from the NASCET nor the one from ECST analyzed data specifically by sex. Although the superiority of carotid endarterectomy (CEA) over the best medical management in protecting against stroke for selected symptomatic and asymptomatic patients with carotid lesions was well demonstrated,3–7 post-hoc analyses,8,9 along with several reviews and large single-center studies, have prompted a reevaluation of the role of CEA in women.10–14 The NASCET results did not distinguish, …

Estrogen deprivation and replacement modulate cerebral capillary density with vascular expression of angiogenic molecules in middle-aged female rats.

The effect of postmenopausal estrogen replacement therapy (ERT) on the risk or severity of cerebrovascular disorders is as yet unclear, and the evidence for flow preservation being a mechanism of estrogen neuroprotection remains elusive. The authors examined whether estrogen-mediated flow-preserving neuroprotective mechanisms, if any, may involve its angiogenic action. This study was conducted using middle-aged (44 weeks) female rats because of the importance of aging in cerebrovascular disease in women. Middle-aged female rats were subjected to sham operation, ovariectomy, or ovariectomy with ERT. The anatomic cerebral capillary morphology showed a significant reduction in the total capillary density in the frontal cortex after ovariectomy. This was associated with marked decreases in protein and gene expression of vascular endothelial growth factor and its angiogenic receptors in cerebral vessels, as demonstrated by immunohistochemistry and hybridization. The expression levels of both estrogen receptor (ER) subtypes, ERalpha and ERbeta, in cerebral vessels were significantly reduced after ovariectomy, but ERbeta was more dramatically downregulated as assessed by the ERbeta/ERalpha ratio. These ovariectomy-induced changes were completely prevented by ERT. Vascular endothelial growth factor appears to be a critical regulatory molecule for physiologic cerebral angiogenesis in middle-aged female rats and may play an important role in the flow-preserving neuroprotective action of estrogen through its angiogenic and antiapoptotic properties.

Acute Cerebrovascular Disease in Women

In 2,000 consecutive stroke patients collected in a prospective hospital-based stroke registry over a 10-year period, we assessed whether stroke in men and women was different in respect to vascular risk factors, clinical features and natural history. The frequency of the different variable in men and women was analyzed by means of univariate analysis and logistic regression models. Women accounted for 48% of the study population (n = 967) and were older than men (mean age 75 vs. 69 years, p < 0.001). In the age group of 85 years or older, stroke was more frequent in women than in men (69.8 vs. 30.2%, p < 0.001). Women showed a higher frequency of cardioembolic infarction and a lower occurrence of lacunar infarction and stroke of undetermined cause than men. In-hospital mortality (17.4 vs. 13.3%) and length of hospital stay (19.6 vs. 16.7 days) was significantly higher (p < 0.001) in women than in men. In the model based on demographic variables and cardiovascular risk factors, obesity, heart failure, atrial fibrillation and age were significant predictors of stroke in women, while intermittent claudication, ischemic heart disease, chronic obstructive pulmonary disease, cigarette smoking and alcohol abuse were predictors in male sex. Hypertension and limb weakness were predictors for stroke in women, and absence of neurological deficit at hospital discharge, lacunar syndrome and ataxia were predictors in men in the models based on all variables. Women differ from men in the distribution of risk factors and stroke subtype, stroke severity and outcome. Differences in stroke pathology and/or differences in functional anatomy or plasticity of the brain between sexes may account for these findings.

A common mutation in lipoprotein lipase confers a 2-fold increase in risk of ischemic cerebrovascular disease in women but not in men.

We previously showed that the common Asn291Ser substitution in lipoprotein lipase is associated with elevated plasma triglyceride levels and a 2-fold increase in the risk of ischemic heart disease in women but not men. In this study, we tested the hypothesis that this substitution is also associated with an increased risk of ischemic cerebrovascular disease (ICVD). We compared 260 patients who had nonfatal ICVD and carotid stenosis >/=50% with 1560 age-matched controls and also compared 205 Copenhagen City Heart Study cases who had nonfatal ICVD with 1210 age-matched controls. All subjects were white and from Denmark. Overall, no significant difference was observed between carrier frequencies among those with and without ICVD; however, sex interacted with genotype in predicting ICVD in the ICVD and carotid stenosis cases (P=0.02). In Copenhagen City Heart Study cases, sex was not significant (P=0.18). Odds ratios for ICVD in female mutation carriers were 2.9 (95% confidence interval [CI], 1.3 to 6. 4) and 1.9 (95% CI, 0.8 to 4.6) in ICVD plus carotid stenosis cases and Copenhagen City Heart Study cases, respectively. Equivalent values in male mutation carriers were 0.8 (95% CI, 0.3 to 1.8) and 0.8 (95% CI, 0.3 to 2.0), respectively. These results were similar in analyses that also allowed for other conventional cardiovascular risk factors. These results suggest that the Asn291Ser substitution in lipoprotein lipase is not associated with nonfatal ICVD in men but that it possibly confers a 2-fold risk in women.

A common mutation in lipoprotein lipase confers a two-fold increase in risk of ischemic cerebrovascular disease in women

A common mutation in lipoprotein lipase confers a two-fold increase in risk of ischemic cerebrovascular disease in women

Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus.

To determine rates of morbidity due to cardiovascular and cerebrovascular diseases among women with systemic lupus erythematosus (SLE). I used the California Hospital Discharge Database, which contains information on all discharges from acute care hospitals in California, to identify women with SLE who had been hospitalized for treatment of either acute myocardial infarction (AMI), congestive heart failure (CHF), or cerebrovascular accident (CVA) from 1991 to 1994. I compared the proportions of hospitalizations for each cause among women with SLE with those in a group of women without SLE, for 3 age strata (18-44 years, 45-64 years, and > or =65 years). Compared with young women without SLE, young women with SLE were 2.27 times more likely to be hospitalized because of AMI (95% confidence interval [95% CI] 1.08-3.46), 3.80 times more likely to be hospitalized because of CHF (95% CI 2.41-5.19), and 2.05 times more likely to be hospitalized because of CVA (95% CI 1.17-2.93). Among middle-aged women with SLE, the frequencies of hospitalization for AMI and CVA did not differ from those of the comparison group, but the risk of hospitalization for CHF was higher (odds ratio [OR] 1.39, 95% CI 1.05-1.73). Among elderly women with SLE, the risk of hospitalization for AMI was significantly lower (OR 0.70, 95% CI 0.51-0.89), the risk of hospitalization for CHF was higher (OR 1.25, 95% CI 1.01-1.49), and the risk of hospitalization for CVA was not significantly different from those in the comparison group. Young women with SLE are at substantially increased risk of AMI, CHF, and CVA. The relative odds of these conditions decrease with age among women with SLE.

Polymorphisms of coagulation/fibrinolysis genes: gene environment interactions and vascular risk

Circulating concentrations of plasminogen activator inhibitor-1 (PAI-1), factor VII and fibrinogen have all been related to vascular risk in large prospective studies. Evidence indicates that all three proteins are increased in the presence of insulin resistance and factor VII and PAI-1 correlate strongly with circulating levels of insulin and lipids. Polymorphisms of the genes coding for PAI-1, factor VII and fibrinogen have been investigated in relation to gene environment interactions and vascular risk. Three polymorphisms have been described in the PAI-1 gene, a 3′ Hind III RFLP, an intronic CA repeat and a 4G/5G insertion deletion 675 bp 5′ of the start site of transcription. The 4G/5G site has been shown to be triglyceride responsive and higher levels of PAI-1 have been reported in subjects homozygous for the 4G allele. Three out of four case control studies have related possession of the 4G/4G genotype to an increased risk of coronary artery disease and our studies in patients undergoing coronary angiography indicate that this is due to increased myocardial infarction rather than atheroma. We have investigated 600 subjects with cerebrovascular disease and found no relationship to the 4G/5G polymorphism. Two major polymorphisms have been identified in the factor VII gene, a promoter decanucleotide repeat and a G-A substitution at codon 353. Evidence indicates that the latter mutation affects factor VII levels by interfering with intracellular processing of the molecule and subjects homozygous for the adenine genotype (M2/M2) have levels of factor VII 20–30% lower than M1/M2 or M1/M1 carriers. Two studies have, however, failed to show a relationship between genotype and cardiovascular disease and we have found no association with cerebrovascular disease. A number of mutations have been described in the genes coding for the alpha, beta and gamma chains of fibrinogen. These polymorphisms are reported to be responsible for from 3% to 50% of circulating levels in various studies and there is evidence that the effect of smoking is genotype specific. In the ECTIM study the beta Bcl I polymorphism has been related to cardiovascular disease and work from our unit has related the Bβ448 polymorphism to the presence of cerebrovascular disease in women. Further prospective studies are warranted to evaluate the role of these genes in disease.

Lifestyle factors and risk of cerebrovascular disease in women. The Copenhagen City Heart Study.

The purpose of the present analysis was to determine how lifestyle influences the risk of cerebrovascular disease in women participating in the Copenhagen City Heart Study. A random sample of a white, lower and middle-class, urban population selected in 1976 was invited to two cardiovascular examinations at 5-year intervals. The present analysis was based on 7060 women invited to an initial examination from 1976 through 1978, aged 35 years or more, and without previous stroke or transient ischemic attack. At the initial examination, potential risk factors were recorded. The 265 first cases of stroke and transient ischemic attack were ascertained at a second examination 5 years later and through hospital records and death certificates through 1988. The Cox regression model was used to estimate the influence of the factors recorded on the risk of cerebrovascular disease. The relative risks of cigarette smoking and lack of physical activity were 1.4 and 1.45; 95% confidence limits, 1.02 to 1.94 and 1.01 to 2.08, respectively). The relative risk of daily consumption of tranquilizers was 1.25 (95% confidence limits, 0.96 to 1.62). No significant influence was found for number of cigarettes, body mass index, or alcohol intake. In postmenopausal women, there was a statistically significant interaction (P < .041) between smoking and hormone replacement therapy. Smokers receiving this therapy had a 28% lower risk of cerebrovascular disease than smokers not receiving it. The statistically significant and equally potent effects on the risk of cerebrovascular disease were found for cigarette smoking and lack of physical activity. The risk associated with smoking seemed to be influenced by hormonal replacement therapy.

STROKES IN WOMEN OF CHILDBEARING AGE. A POPULATION STUDY

Schoenberg, Bruce S.; Whisnant, Jack P.; Taylor, William F.; Kempers, Roger D. Author Information

Strokes in women of childbearing age. A population study.

The indidence of cerebrovascular disease in women of childbearing age (15-49 years) in Rochester Minnesota from 1955 through 1960 (before oral contraceptive use) and from 1961 through 1966 (during OC general use) was studied. Data were compared with the period 1945 through 1954. From 1945-1954 there were 14 cases of cerebrovascular disease and 30 cases from 1955-1966. Only 1 patient in the study was taking an oral contraceptive at the time of the stroke. The incidence of all types of strokes increased with increasing age of the patients. The general incidence rate for strokes for women (per 100000 per year) was 27.9 from 1955-1960 and 17.2 from 1961-1966 a difference that is not statistically significant.