Risk Of Disease In Women Research Articles

Cardiovascular disease and dyslipidemia in women.

Cardiovascular disease, primarily coronary heart disease (CHD), outnumbers the next 16 causes of death in women combined. However, the long-held belief that heart disease in women has a more benign prognosis than in men has resulted in less aggressive diagnosis and management patterns. Appreciation of the differences between men and women in CHD risk factors and presentation can assist in treatment decisions. Although estrogen replacement offers substantial beneficial effects on lipid levels in postmenopausal women, the first 2 randomized trials of estrogen alone and estrogen plus progestin, the Heart and Estrogen/Progestin Replacement Study and Estrogen Replacement and Atherosclerosis Study, observed no benefit in reducing risk of CHD death and nonfatal myocardial infarction and angiographic progression of CHD, respectively, in women with CHD. Available data show that lipid-lowering therapy reduces women's CHD risk and mortality but also indicate that a considerable proportion of women remains untreated or undertreated. Randomized trials of statins for primary and secondary prevention of coronary heart disease suggest that these agents are at least as effective for lowering coronary disease risk in women as in men. Therefore, statin drugs should be the drug of first choice for women with established CHD. Hypercholesterolemic postmenopausal women who require estrogen for menopausal symptoms may derive further reductions in low-density lipoprotein cholesterol and reductions in trigyceride levels with the addition of a statin drug.

Homocysteine in postmenopausal women and the importance of hormone replacement therapy.

Homocysteine (Hcy) has been shown to damage the vascular endothelial cells, contributing to atherothrombosis. The increase in plasma Hcy levels with natural menopause suggests a close relationship between Hcy metabolism and estrogen status and proposes one of the mechanisms through which menopause unfavorably affects cardiovascular disease risk in women. In addition to the prevention of osteoporosis, hormone replacement therapy (HRT) lowers Hcy levels in postmenopausal women. The first report by van der Mooren et al., demonstrated in an uncontrolled study a significant reduction (11%) in fasting serum Hcy level after 6 months of treatment with sequentially combined estradiol-dydrogesterone therapy in 21 healthy postmenopausal women. This effect was particularly evident in women with initially elevated baseline serum Hcy concentrations. Similar results were found in other studies in which women were treated with various transdermal as well as oral HRT regimens, although two studies could not confirm these findings. All these studies were uncontrolled, and three of them consisted of a relatively small number of participants. Therefore, they remained inconclusive. Three randomized controlled trials on HRT and Hcy were published to date, confirming that postmenopausal HRT reduces circulating levels of Hcy. Current and recent HRT use is associated with a slight increased risk of breast cancer. As a result of this, research has centered on finding compounds that can prevent the consequences of estrogen deficiency, without the potential risk of HRT. Raloxifene, referred to as a Selective Estrogen Receptor Modulator (SERM), has the potential as a viable alternative to HRT. Recently, two randomized controlled trials demonstrated that raloxifene lowers plasma Hcy levels in postmenopausal women, similar to the reduction obtained with HRT. Little is known about the mechanisms underlying the HRT-associated lowering of plasma Hcy. Proposed mechanisms relate to an increase in kidney methionine synthase activity or may be related to the transamination of methionine. We conclude that HRT decreases plasma Hcy levels in postmenopausal women and that the strongest reductions can be achieved in women with the highest concentrations.

Cervical screening in England and Wales: its effect has been underestimated.

Opinions about cervical screening in the UK tend to follow one of two negative lines of thought. The first is that cervical cancer is a rare disease, and too much time and effort are spent on screening. The second is that it has been relatively ineffective, since incidence of invasive carcinoma did not fall until the NHS Cervical Screening Programme (NHSCSP) was introduced in 1988, although it fell by 40% since then. This paper presents publicly available data to demonstrate that neither of these views is true. Registrations of invasive carcinoma of the uterine cervix and carcinoma in situ in England and Wales between 1971 and 1996 show that a substantially increased risk of disease in women born since 1940 has been reversed, almost certainly by greatly improved screening. Cervical carcinoma is now a rare disease because most cases are prevented before they become invasive, mostly by screening young women, aged 20-40, before the decade of life when symptomatic cervical carcinoma most frequently presents.

The effect of type 1 diabetes mellitus on the gender difference in coronary artery calcification

OBJECTIVESTo examine whether the gender difference in coronary artery calcification, a measure of atherosclerotic plaque burden, is lost in type 1 diabetic patients, and whether abnormalities in established coronary heart disease risk factors explain this.BACKGROUNDType 1 diabetes abolishes the gender difference in coronary heart disease mortality because it is associated with a greater elevation of coronary disease risk in women than men. The pathophysiological basis of this is not understood.METHODSCoronary artery calcification and coronary risk factors were compared in 199 type 1 diabetic patients and 201 nondiabetic participants of similar age (30 to 55 years) and gender (50% female) distribution. Only one subject had a history of coronary disease. Calcification was measured with electron beam computed tomography.RESULTSIn nondiabetic participants there was a large gender difference in calcification prevalence (men 54%, women 21%, odds ratio 4.5, p < 0.001), half of which was explained by established risk factors (odds ratio after adjustment = 2.2). Diabetes was associated with a greatly increased prevalence of calcification in women (47%), but not men (52%), so that the gender difference in calcification was lost (p = 0.002 for the greater effect of diabetes on calcification in women than men). On adjustment for risk factors, diabetes remained associated with a threefold higher odds ratio of calcification in women than men (p = 0.02).CONCLUSIONSIn type 1 diabetes coronary artery calcification is greatly increased in women and the gender difference in calcification is lost. Little of this is explained by known coronary risk factors.

Serum Testosterone Levels Decrease in Middle Age in Women With the Polycystic Ovary Syndrome

Abstract Objective: To determine whether testosterone levels change as women with the polycystic ovary syndrome (PCOS) grow older. Design: A follow-up cross-sectional study of a cohort of women with PCOS identified up to 20–25 years ago. Setting: Women with PCOS were recruited primarily from practice records between 1970 and 1990. Voter registration tapes and household directories were used to identify age-, race-, and neighborhood-matched controls. Participant(s): Eighty-four women with PCOS, 20–57 years of age, and 37 age-matched controls participating in a study of the risk for cardiovascular disease in women with PCOS. Intervention(s): Clinical data were collected by questionnaire and fasting blood samples were obtained randomly throughout the menstrual cycle. Main Outcome Measure(s): Total and non–SHBG-bound testosterone levels. Result(s): Total and non–SHBG-bound testosterone levels were similar in women with PCOS who were 20–42 years of age but were reduced by approximately 50% among women 42–47 years of age and remained stable in women older than 47 years of age. Testosterone levels were increased in younger and older women with PCOS compared with controls but were similar to controls in women 42–47 years of age. Conclusion(s): Hyperandrogenism partly resolves before menopause in women with PCOS. This change may explain the tendency of women with PCOS to cycle regularly as they grow older. Testosterone levels remain elevated in older women with PCOS, however, and may contribute to their increased risk for cardiovascular disease, endometrial cancer, and other diseases.

Job stress and the occupational gradient in coronary heart disease risk in women: The Stockholm Female Coronary Risk Study

Recent studies of men have shown that job stress is important in understanding the occupational gradient in coronary heart disease (CHD), but these relationships have rarely been studied in women. With increasing numbers of women in the workforce it is important to have a more complete understanding of how CHD risk may be mediated by job stress as well as other biological and behavioural risk factors. The objective of this study was to examine the occupational gradient in CHD risk in relation to job stress and other traditional risk factors in currently employed women. We used data from the Stockholm Female Coronary Risk Study, a population based case-control study, comprising 292 women with CHD aged 65 years or younger and 292 age-matched healthy women (controls). An inversely graded association was observed between occupational class and CHD risk. Compared with the highest (executive/professional), women in the lowest occupational class (semi/unskilled) had a four-fold (95% CI 1.75–8.83) increased age-adjusted risk for CHD. Simultaneous adjustment for traditional risk factors and job stress attenuated this risk to 2.45 (95% CI 1.01–6.14). Neither job control nor the Karasek demand-control model of job stress substantially explained the increased CHD risk of women in the lowest occupational classes. It is likely that lower occupational class working women face multiple and sometimes interacting sources of work and non-work stress that are mediated by behavioural and biological factors that increase their CHD risk.

Weight Loss is Correlated with an Improved Lipoprotein Profile in Obese Postmenopausal Women

Background: Changes in plasma lipid and lipoprotein distributions that occur after menopause increase the risk of cardiovascular disease in women, especially in those who are overweight.Objective: The purpose of this study was to evaluate the impact of a nine-month weight reduction program on plasma lipids, dietary intake and abdominal fat obesity.Design: A partial crossover design was used to study a weight loss treatment consisting of Phentermine hydrochloride (Fastin®, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) therapy plus a low energy diet (5040 kJ/d). Forty-seven obese, postmenopausal Caucasian women (BMI of 30–38 kg/m2) were randomized into two groups, both of which received drug and diet treatment over six months. However, Group I started the intervention program three months later than Group II. Plasma total, HDL and LDL cholesterol and triacylglycerol were measured, body composition was assessed by anthropometry and dual energy x-ray absorptiometry, and food frequency records were collected at four timepoints.Results: Over nine months, women in Group II reduced body weight (14.4%), lowered plasma concentrations of LDL cholesterol (14% to 26%) and triacylglycerol (15%) and raised plasma HDL cholesterol concentration (15%). These plasma lipid changes decreased the total cholesterol/HDL cholesterol ratio from 4.3 to 3.2. All subjects decreased abdominal fat measurements and energy and cholesterol intakes, as well as percentage of energy derived from total and saturated fat during the study. Most subjects also increased dietary fiber consumption.Conclusion: Both weight loss and diet modifications are associated with an improved plasma lipid profile in obese postmenopausal women.

Prevention of Heart Disease in Women: Recommendations for Management of Risk Factors

Coronary heart disease is the leading cause of death and disability in women in the U.S. Unfortunately, efforts for primary and secondary prevention of coronary heart disease are less than optimal. The need to emphasize prevention of coronary heart disease in women in important because first events are often fatal in women. Factors that are unique in terms of their influence on risk for coronary heart disease in women include age, reproductive and hormonal status, high density lipoprotein cholesterol and triglyceride levels, and the presence of diabetes. A consistent plan to address risk factor management of each woman is the key to long term risk reduction. Nurses and nurse practitioners, working in any setting, can use the recommendations presented in this paper to help women reduce their risk for coronary heart disease.

Epidemiology of hypertriglyceridemia and cardiovascular disease

Epidemiologic studies provide increasing evidence that hypertriglyceridemia is a risk factor for cardiovascular disease. A meta-analysis of 17 population-based studies of triglyceride levels and cardiovascular disease identified a 76% increase in cardiovascular disease risk in women and a 31% increase in men associated with a 1 mmol/L increase in triglyceride levels. Additional epidemiologic studies have shown that plasma triglyceride levels and low-density lipoprotein particle size predict subsequent coronary artery disease. Taken together, the existing epidemiologic data may help identify a group of patients who may benefit from interventions aimed at decreasing triglyceride levels associated with an increased risk of cardiovascular disease.

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

BRCA1 and BRCA2: mutations and other genetic changes--practical relevance

Genetic predisposition is responsible for 5-10% of all breast cancer. Within the past 10 years the major susceptibility genes for breast cancer, BRCA1 and BRCA2, have been identified. Both genes are considered to be tumor-suppressor genes, but their function is poorly understood. Current genetic testing for mutated BRCA1 and BRCA2 is the basis for estimating disease risk for women with a strong family history of breast cancer and will provide important information on the prevention and treatment of familial breast cancer.

Complex relation between increasing fat mass and decreasing high density lipoprotein cholesterol levels: evidence from a population-based study of premenopausal women.

High density lipoprotein (HDL) cholesterol levels can be used to predict cardiovascular disease risk in women. To better understand variability in HDL cholesterol levels, the authors examined the relation with three domains (body size and type, sex hormone status, and carbohydrate metabolism) in a cross-sectional population-based 1993-1994 study of 402 premenopausal women from Tecumseh, Michigan. They found that these domains explained 27% of the total variation in HDL cholesterol levels; waist-to-hip ratio was the term that explained the highest proportion of variability (6% after fat mass, sex hormone binding globulin, and insulin levels were added to the model). In analyses restricted to women whose body mass index was > or = 32 kg/m2, which constituted 19% of this population, neither body mass index nor fat mass was a significant predictor of variability in HDL cholesterol levels. Significant variables were insulin levels, waist-to-hip ratio, and smoking. This finding suggests that there is a saturation of the relation between increasing fat mass and lower HDL cholesterol levels, as evidenced by the lack of a relation between the two among the heaviest women. Meanwhile, among the heaviest women, increasing insulin levels and a higher waist-to-hip ratio remained predictors of low levels of HDL cholesterol.

Addressing coronary heart disease risk in women.

Contrary to popular perceptions, coronary heart disease (CHD) is a serious and widespread problem in US women. Public education, preventive interventions, and better data on CHD risk and prevention in women are needed.

Dietary intake of monounsaturated and polyunsaturated fats reduced risk for coronary disease in women

Dietary intake of monounsaturated and polyunsaturated fats reduced risk for coronary disease in women

Dietary Fat Intake and the Risk of Coronary Heart Disease in Women

Dietary Fat Intake and the Risk of Coronary Heart Disease in Women

How to Estimate and Reduce Coronary Heart Disease Risk in Women

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Effects of short-term hormone replacement therapies on low-density lipoprotein metabolism in cynomologus monkeys.

Estrogen replacement therapy reduces the risk of coronary heart disease in women and decreases the extent of atherosclerosis in monkeys. In our previous studies, estrogen treatment decreased arterial LDL degradation and accumulation, thus indicating one mechanism by which estrogen inhibits the progression of atherosclerosis. The influence of progestins on these processes remains nuclear. The objective of this study was to determine the effects of oral estrogen (conjugated equine estrogens) and progestin (medroxyprogesterone acetate) alone or in combination on arterial LDL metabolism after 12 weeks of atherogenic stimulus. This relatively short period of treatment was chosen to determine effects on arterial LDL metabolism before substantial subendothelial macrophage accumulation. In contrast to previous studies (16 to 18 weeks of treatment), when macrophages were present in the intima, neither estrogen nor progestin (nor their combination) had any effect on any index of arterial LDL metabolism. These results suggest that estrogen may preferentially reduce LDL metabolism in macrophages with little effect on cells of the normal artery. In contrast to arterial LDL metabolism, hepatic LDL uptake was significantly increased in animals treated with estrogen or estrogen plus progestin. Despite the increased LDL uptake by the liver, hepatic lipid content was significantly decreased by approximately 50% in both estrogen and estrogen-plus-progestin treatment compared with control and progestin-treated animals. The decrease in hepatic cholesterol content in hypothesized to be due to increased biliary secretion of cholesterol.

Breast prostheses and their complications

In the past few years silicone breast implants have been a highly charged and controversial topic for psychologic, health and politico-legal reasons for patients and for surgical, medical and research concern for professionals. Both sides are interested in knowing about the complications encountered with these implants on one hand and to find the ideal device needed for mammary reconstruction on the other. Indeed silicone does not fulfill the characteristics initially expected for a synthetic soft-tissue substitute. The local cellular response leads to the formation of a capsule around the implant with frequently unsatisfying cosmetic results. The well described leakage occurring through the silicone envelope allows the silicone gel to diffuse to multiple anatomic areas in the body. Scientific works demonstrated that silicone gel acts as a potent immunologic adjuvant and can induce antibodies to silicone surface-associated antigens. Breast implanted women who present with systemic clinical symptoms can be included either in the group of well defined connective tissue diseases or in the atypical connective tissue disease-like syndrome. The largest epidemiologic studies have shown reassuring evidence against large hazards but have documented a low but statistically significant risk of connective-tissue diseases in women with silicone gel filled implants. Practitioners must manage these patients with the awareness that reliable objective tests to identify the useful problem are not yet available.

Breast Implants and Connective-Tissue Disease

To the Editor. —The Women's Health Study described by Dr Hennekens and colleagues 1 reported a 24% increase in the risk of connective-tissue disease in women with breast implants. However, the authors failed to consider an important point—the possibility of selection bias into the study of only the healthiest women. The consent form of the study requires that the participants had to agree to not take aspirin or other drugs with aspirinlike effects for 5 years. Any women with connective-tissue disease or chronic pain would have difficulty agreeing to this study condition. Aching joints and muscles are frequent complaints of women with breast implants and are usually self-medicated with these drugs. The effect of this condition would be a strong self-selection bias out of the study. A woman may not return the questionnaire once she had read the consent form—indeed, less than 25% responded. A large underestimate of the actual

Physical inactivity and cardiovascular disease risk in women

Physical inactivity and cardiovascular disease risk in women