Incident Coronary Heart Disease In Women Research Articles

THE EFFECT OF DYSLIPIDEMIA ON THE INCIDENCE OF CORONARY HEART DISEASE IN WOMEN

Coronary heart disease (CHD) is one of the non-communicable diseases that causes the highest mortality in the world. Dyslipidemia is an important risk factor for CHD. This study aims to determine the relationship of dyslipidemia in detail including increased cholesterol, increased triglycerides, increased LDL cholesterol and decreased HDL cholesterol on the incidence of CHD in women at PKU Muhammadiyah Hospital Yogyakarta. This study used a case-control design involving 58 women as research subjects. The case group consisted of 29 women diagnosed with CHD and the control group consisted of 29 women diagnosed as non-CHD patients, including chronic lung disease, pneumonia, heart failure, dyspepsia and malignancy. Data tracing through medical records was carried out in March-September 2019. The results of this study the age range in the case group was 45-84 years and in the control group was 42-90 years. Based on the Chi-Square test, there was a significant relationship between dyslipidemia (RO = 7.04 (1.73-28.6), p = 0.003), high total cholesterol levels (RO = 5.14 (1.54-17.2), p = 0.012), high LDL cholesterol levels (RO = 9.286 (2.29-37.6), p = 0.001) and the incidence of CHD in women. From the Chi-Square test there was no significant relationship between high triglyceride levels (OR=2.16 (CI:0.62-7.49), p=0.358), low HDL cholesterol levels (RO=2,554 (0.83-7.84), p=0.167) and CHD incidence in women. The conclusion of this study is the effect of dyslipidemia including increased cholesterol and LDL cholesterol on the incidence of CHD in women at PKU Muhammadiyah Hospital Yogyakarta.

Associations of Job Strain, Stressful Life Events, and Social Strain With Coronary Heart Disease in the Women's Health Initiative Observational Study.

BackgroundThe association between psychosocial stress and coronary heart disease (CHD) may be stronger in women than men and may differ across types of stressors. In this study, we assessed associations of psychosocial stressors, including job strain, stressful life events, and social strain with the incidence of CHD in women.Methods and ResultsWe used longitudinal data from 80 825 WHI‐OS (Women's Health Initiative Observational Study) participants with a mean age of 63.4 years (7.3 years) at baseline. Job strain was assessed through linkage of Standard Occupational Classification codes to the Occupational Information Network. Stressful life events and social strain were assessed via validated self‐reported questionnaires. Cox proportional hazard models were used to evaluate associations of each stressor with CHD separately and jointly. A total of 3841 (4.8%) women developed CHD during an average of 14.7 years of follow‐up. After adjustment for age, other stressors, job tenure, and socioeconomic factors, high stressful life events score was associated with a 12% increased CHD risk, and high social strain was associated with a 9% increased CHD risk. Job strain was not independently associated with CHD risk, but we observed a statistically significant interaction between job strain and social strain (P=0.04), such that among women with high social strain, passive job strain was associated with a 21% increased CHD risk.ConclusionsHigh stressful life events and social strain were each associated with higher CHD risk. Job strain and social strain work synergistically to increase CHD risk.

Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women

Risk profiles for premature coronary heart disease (CHD) are unclear. To examine baseline risk profiles for incident CHD in women by age at onset. A prospective cohort of US female health professionals participating in the Women's Health Study was conducted; median follow-up was 21.4 years. Participants included 28 024 women aged 45 years or older without known cardiovascular disease. Baseline profiles were obtained from April 30, 1993, to January 24, 1996, and analyses were conducted from October 1, 2017, to October 1, 2020. More than 50 clinical, lipid, inflammatory, and metabolic risk factors and biomarkers. Four age groups were examined (<55, 55 to <65, 65 to <75, and ≥75 years) for CHD onset, and adjusted hazard ratios (aHRs) were calculated using stratified Cox proportional hazard regression models with age as the time scale and adjusting for clinical factors. Women contributed to different age groups over time. Of the clinical factors in the women, diabetes had the highest aHR for CHD onset at any age, ranging from 10.71 (95% CI, 5.57-20.60) at CHD onset in those younger than 55 years to 3.47 (95% CI, 2.47-4.87) at CHD onset in those 75 years or older. Risks that were also noted for CHD onset in participants younger than 55 years included metabolic syndrome (aHR, 6.09; 95% CI, 3.60-10.29), hypertension (aHR, 4.58; 95% CI, 2.76-7.60), obesity (aHR, 4.33; 95% CI, 2.31-8.11), and smoking (aHR, 3.92; 95% CI, 2.32-6.63). Myocardial infarction in a parent before age 60 years was associated with 1.5- to 2-fold risk of CHD in participants up to age 75 years. From approximately 50 biomarkers, lipoprotein insulin resistance had the highest standardized aHR: 6.40 (95% CI, 3.14-13.06) for CHD onset in women younger than 55 years, attenuating with age. In comparison, weaker but significant associations with CHD in women younger than 55 years were noted (per SD increment) for low-density lipoprotein cholesterol (aHR, 1.38; 95% CI, 1.10-1.74), non-high-density lipoprotein cholesterol (aHR, 1.67; 95% CI, 1.36-2.04), apolipoprotein B (aHR, 1.89; 95% CI, 1.52-2.35), triglycerides (aHR, 2.14; 95% CI, 1.72-2.67), and inflammatory biomarkers (1.2- to 1.8-fold)-all attenuating with age. Some biomarkers had similar CHD age associations (eg, physical inactivity, lipoprotein[a], total high-density lipoprotein particles), while a few had no association with CHD onset at any age. Most risk factors and biomarkers had associations that attenuated with increasing age at onset. In this cohort study, diabetes and insulin resistance, in addition to hypertension, obesity, and smoking, appeared to be the strongest risk factors for premature onset of CHD. Most risk factors had attenuated relative rates at older ages.

Association of lipid markers with coronary heart disease and stroke mortality: A 15-year follow-up study.

Objective(s):It has been proposed that lipid markers may predict cardiovascular events; however, their effect may vary depending on the type of cardiovascular disease. The purpose of this study was to investigate the effects of lipid markers on death from coronary heart disease (CHD) and stroke in competing risks setting.Materials and Methods:Participants included 2502 women and 2020 men, age 40 years or older from Tehran Lipid and Glucose Study. The association between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) with hazard and cumulative incidence of CHD and stroke was investigated using cause-specific hazard and sub-distribution hazard models. Statistical analyses were performed using “risk regression” and “cmprsk” package in R 3.3.2.Results:One standard deviation (SD) increase in TC and LDL-C increased the hazard of CHD death by 1.42 (CI=1.07,1.89) and 1.41 (CI=1.04,1.93), respectively. 1-SD increase in TG increased the cumulative incidence of CHD death increased by 1.94 (CI=1.02,3.75) in women. Other risk factors were not associated with the hazard and cumulative incidence of CHD in women, men and the total sample. In addition, none of lipids had a significant effect on the hazard and cumulative incidence of stroke in men, women and the total sample.Conclusion:The associations of lipid components on CHD death were modified by gender. TC, LDL-C and TG were independent predictors of CHD mortality in women. Furthermore, death due to stroke changes the association of lipid markers with CHD mortality.

Social Integration and Reduced Risk of Coronary Heart Disease in Women: The Role of Lifestyle Behaviors.

Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and whether associations differ by case fatality are unclear. This study sought to examine the associations between social integration and risk of incident CHD in a large female prospective cohort. Seventy-six thousand three hundred and sixty-two women in the Nurses' Health Study, free of CHD and stroke at baseline (1992), were followed until 2014. Social integration was assessed by a simplified Berkman-Syme Social Network Index every 4 years. End points included nonfatal myocardial infarction and fatal CHD. Two thousand three hundred and seventy-two incident CHD events occurred throughout follow-up. Adjusting for demographic, health/medical risk factors, and depressive symptoms, being socially integrated was significantly associated with lower CHD risk, particularly fatal CHD. The most socially integrated women had a hazard ratio of 0.55 (95% confidence interval, 0.41-0.73) of developing fatal CHD compared with those least socially integrated (P for trend <0.0001). When additionally adjusting for lifestyle behaviors, findings for fatal CHD were maintained but attenuated (P for trend =0.02), whereas the significant associations no longer remained for nonfatal myocardial infarction. The inverse associations between social integration and nonfatal myocardial infarction risk were largely explained by health-promoting behaviors, particularly through differences in cigarette smoking; however, the association with fatal CHD risk remained after accounting for these behaviors and, thus, may involve more direct biological mechanisms. Social integration is inversely associated with CHD incidence in women, but is largely explained by lifestyle/behavioral pathways.

Genetic Research and Women's Heart Disease: a Primer.

Purpose of ReviewThis review provides a brief synopsis of sexual dimorphism in atherosclerosis with an emphasis on genetic studies aimed to better understand the atherosclerotic process and clinical outcomes in women. Such studies are warranted because development of atherosclerosis, impact of several traditional risk factors, and burden of coronary heart disease (CHD) differ between women and men.Recent FindingsWhile most candidate gene studies pool women and men and adjust for sex, some sex-specific studies provide evidence of association between candidate genes and prevalent and incident CHD in women. So far, most genome-wide association studies (GWAS) also failed to consider sex-specific associations. The few GWAS focused on women tended to have small sample sizes and insufficient power to reject the null hypothesis of no association even if associations exist.SummaryFew studies consider that sex can modify the effect of gene variants on CHD. Sufficiently large-scale genetic studies in women of different race/ethnic groups, taking into account possible gene-gene and gene-environment interactions as well as hormone-mediated epigenetic mechanisms, are needed. Using the same disease definition for women and men might not be appropriate. Accurate phenotyping and inclusion of relevant outcomes in women, together with targeting the entire spectrum of atherosclerosis, could help address the contribution of genes to sexual dimorphism in atherosclerosis. Discovered genetic loci should be taken forward for replication and functional studies to elucidate the plausible underlying biological mechanisms. A better understanding of the etiology of atherosclerosis in women would facilitate future prevention efforts and interventions.

Depression is a risk factor for incident coronary heart disease in women: An 18-year longitudinal study

BackgroundAccording to a recent position paper by the American Heart Association, it remains unclear whether depression is a risk factor for incident Coronary Heart Disease (CHD). We assessed whether a depressive disorder independently predicts 18-year incident CHD in women. MethodA prospective longitudinal study of 860 women enrolled in the Geelong Osteoporosis Study (1993–2011) was conducted. Participants were derived from an age-stratified, representative sample of women (20–94 years) randomly selected from electoral rolls in South-Eastern Australia. The exposure was a diagnosis of a depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Outcomes data were collected from hospital medical records: (1) Primary outcome: a composite measure of cardiac death, non-fatal Myocardial Infarction or coronary intervention. (2) Secondary outcome: any cardiac event (un/stable angina, cardiac event not otherwise defined) occurring over the study period. ResultsSeven participants were excluded based on CHD history. Eighty-three participants (9.6%) recorded ≥1 cardiac event over the study period; 47 had a diagnosis that met criteria for inclusion in the primary analysis. Baseline depression predicted 18-year incidence, adjusting for (1) anxiety (adj. OR:2.39; 95% CIs:1.19–4.82), plus (2) typical risk factors (adj. OR:3.22; 95% CIs:1.45–6.93), plus (3) atypical risk factors (adj. OR:3.28; 95% CIs:1.36–7.90). This relationship held when including all cardiac events. No relationship was observed between depression and recurrent cardiac events. ConclusionThe results of this study support the contention that depression is an independent risk factor for CHD incidence in women. Moreover, the strength of association between depression and CHD incidence was of a greater magnitude than any typical and atypical risk factor.

Associations of adiponectin and leptin with incident coronary heart disease and ischemic stroke in african americans: the jackson heart study.

Background: Because the predictive significance of previously reported racial differences in leptin and adiponectin levels remains unclear, we assessed the prospective association of these adipokines with the risk of cardiovascular disease (CVD) events in African Americans, a population with a high prevalence of cardiometabolic risk factors.Methods: Serum specimens from 4,571 Jackson Heart Study participants without prevalent CVD at baseline examination (2000–2004) were analyzed for adiponectin and leptin levels. Cox proportional hazard regression models were used to estimate the associations of the two adipokines with incident coronary heart disease (CHD) and incident ischemic stroke.Results: During 6.2 years average of follow-up, 98 incident CHD and 87 incident ischemic stroke events were documented. Among study participants (64% women; mean age 54 ± 13 years), the mean (standard deviation, SD) was 6.04 (4.32) μg/mL in women and 4.03 (3.14) μg/mL in men for adiponectin and 37.35 (23.90) ng/mL in women and 11.03 (10.05) ng/mL in men for leptin. After multivariable adjustment that included age, body mass index, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, insulin resistance by homeostasis model assessment for insulin resistance, systolic blood pressure, hypertension medication, smoking, and physical activity, adiponectin was directly associated in women with incident stroke, HR = 1.41 (1.04–1.91) per one SD increase (p = 0.03), but not in men (p = 0.42). It was not associated with incident CHD in women or men. Leptin was not associated with incident CHD or incident stroke.Conclusion: In the largest community-based African American cohort, adiponectin was associated among women with a higher risk of incident stroke. Whether adiponectin harbors harmful properties, or it is produced in response to vascular inflammation to counter the atherosclerotic process, or the putative “adiponectin resistance” phenomenon acts, should be further assessed.

Men’s and Women’s Health Beliefs Differentially Predict Coronary Heart Disease Incidence in a Population-Based Sample

To examine gender differences in the association between beliefs in heart disease preventability and 10-year incidence of coronary heart disease (CHD) in a population-based sample. A total of 2,688 Noninstitutionalized Nova Scotians without prior CHD enrolled in the Nova Scotia Health Study (NSHS95) and were followed for 10 years. Risk factors, health behaviors, and incident CHD were assessed. Participants responded "yes" or "no" to a question about heart disease preventability. Survival models, adjusted for age, income, total and high-density lipoprotein cholesterol, and systolic blood pressure, were used to estimate the relation between health belief and incident CHD. Gender differences in the relation between health beliefs and health behaviors were assessed. Gender was a significant moderator of the relation between belief and CHD incidence; specifically, women who believed heart disease could be prevented were less likely to have incident CHD events compared with women who believed heart disease could not be prevented (hazard ratio [HR] = 0.36, 95% confidence interval [CI] = 0.24-0.55, p < .001). This relation was not found for men. Belief was also related to smoking behavior for women (β = -0.70, odds ratio [OR] = 0.50, 95% CI = 0.33-0.74, p = .001) but not for men. Smoking significantly mediated the relation between health beliefs and incident CHD for women (z = -1.96, p = .05), but not for men. Health belief in prevention and subsequent smoking was an important independent predictor of incident CHD in women but not in men.

Temporal trends in the incidence and recurrence of hospitalised atherothrombotic disease in an Australian population, 2000–07: data linkage study

ObjectivesTo examine temporal trends in the incidence and recurrence of hospitalised coronary heart disease (CHD), cerebrovascular disease (CeVD) and peripheral arterial disease (PAD) separately and combined, and by the history...

HFE gene mutations increase the risk of coronary heart disease in women.

The purpose of the present study is to examine HFE gene mutations in relation to newly diagnosed (incident) coronary heart disease (CHD). In a population-based follow-up study of 7,983 individuals aged 55 years and older, we compared the risk of incident CHD between HFE carriers and non-carriers, overall and stratified by sex and smoking status. HFE mutations were significantly associated with an increased risk of incident CHD in women but not in men (hazard ratio [HR] for women = 1.7, 95% confidence interval [CI] 1.2–2.4 versus HR for men = 0.9, 95% CI 0.7–1.2). This increased CHD risk associated with HFE mutations in women was statistically significant in never smokers (HR = 1.8, 95% CI 1.1–2.8) and current smokers (HR = 3.1, 95% CI 1.4–7.1), but not in former smokers (HR = 1.3, 95% CI 0.7–2.4). HFE mutations are associated with increased risk of incident CHD in women.

Meta-analysis: Retinal Vessel Caliber and Risk for Coronary Heart Disease

Retinal vessel caliber may be a novel marker of coronary heart disease (CHD) risk. However, the sex-specific effect, magnitude of association, and effect independent of traditional CHD disease risk factors remain unclear. To determine the association between retinal vessel caliber and risk for CHD. Relevant studies in any language identified through MEDLINE (1950 to June 2009) and EMBASE (1950 to June 2009) databases. Studies were included if they examined a general population, measured retinal vessel caliber from retinal photographs, and documented CHD risk factors and incident CHD events. 6 population-based prospective cohort studies provided data for individual participant meta-analysis. Proportional hazards models, adjusted for traditional CHD risk factors, were constructed for retinal vessel caliber and incident CHD in women and men. Among 22,159 participants who were free of CHD and followed for 5 to 14 years, 2219 (10.0%) incident CHD events occurred. Retinal vessel caliber changes (wider venules and narrower arterioles) were each associated with an increased risk for CHD in women (pooled multivariable-adjusted hazard ratios, 1.16 [95% CI, 1.06 to 1.26] per 20-microm increase in venular caliber and 1.17 [CI, 1.07 to 1.28] per 20-microm decrease in arteriolar caliber) but not in men (1.02 [CI, 0.94 to 1.10] per 20-microm increase in venular caliber and 1.02 [CI, 0.95 to 1.10] per 20-microm decrease in arteriolar caliber). Women without hypertension or diabetes had higher hazard ratios. Error in the measurement of retinal vessel caliber and Framingham variables was not taken into account. Retinal vessel caliber changes were independently associated with an increased risk for CHD events in women.

Relation of Adult-Onset Asthma to Coronary Heart Disease and Stroke

Asthma was associated with atherosclerotic disease in several studies, with evidence that this association may be limited to women. However, most previous studies failed to account for the heterogeneity of asthma subtypes. We previously reported increased carotid intima-medial thickness in women with adult-onset asthma. In this study, the association of adult- and child-onset asthma with incident coronary heart disease (CHD) and stroke were examined. Subjects were classified according to self-report of physician-diagnosed asthma and age of asthma onset. Cox proportional hazards models were used to test the association of adult- and child-onset asthma with incident CHD and stroke, testing for gender interaction. Subanalysis was also performed using only never smokers. Women with adult-onset asthma experienced a 2-fold increase in incident CHD and stroke that was independent of other risk factors, including smoking, body mass index, and physical activity, and persisted when analysis was restricted to never smokers. No significant association was found in women with child-onset asthma or in men. In conclusion, adult-onset asthma may be a significant risk factor for CHD and stroke in women, but not men.

Comparison of the Prognostic Significance of the Electrocardiographic QRS/T Angles in Predicting Incident Coronary Heart Disease and Total Mortality (from the Atherosclerosis Risk In Communities Study)

Spatial QRS/T angle and spatial T-wave axis were shown to be strong independent predictors of incident coronary heart disease (CHD) and total mortality, but they are not routinely available. We evaluated whether frontal plane QRS/T angle, easily obtained as the difference between frontal plane axes of QRS and T, provides a suitable substitute for spatial QRS/T angle as a risk predictor. Our study consisted of 13,973 participants from the ARIC Study. Outcome variables were incident CHD and total mortality during a median follow-up of 14 years. Electrocardiographic variables were categorized as abnormal (>/=95th percentile), borderline (>/=75th and <95th percentile), and normal (<75th percentile) separately for men and women. Cox regression was used to assess the effect of electrocardiographic variables on risk of each outcome. The normal category was considered the reference cell. With adjustment for demographic and clinical characteristics, both QRS/T angles were approximately equally strong predictors of total mortality with >50% increased risk. Spatial QRS/T angle was a stronger predictor of incident CHD in women, with a 114% increased risk, but it was not significantly associated with risk of incident CHD in men. Similarly, frontal plane QRS/T angle was statistically significant for only women with a 74% increased risk of incident CHD. In conclusion, frontal plane QRS/T angle as an easily derived risk measure is a suitable clinical substitute for spatial QRS/T angle for risk prediction.

Seasonal variation in coronary heart disease in Scotland.

Seasonality of coronary heart disease (CHD) was examined to determine whether fatal and non-fatal disease have the same annual rhythm. Time series analysis was carried out on retrospective data over a 10 year period and analysed by age groups ( < 45 to > 75 years) and gender. Data by month were obtained for the years 1962-71. The Registrar General provided information on deaths and the Research and Intelligence Unit of the Scottish Home and Health Department on hospital admissions. In Scotland, between 1962 and 1971, 123 000 patients were admitted to hospital for CHD, of whom 29 000 died. There were a further 97 000 CHD deaths outside hospital. These two groups were also examined as one (coronary incidence) - that is, all coronary deaths and coronary admissions discharged alive. STATISTICAL ANALYSIS AND MAIN RESULTS: Where there was a single annual peak, the sine curve was analysed by cosinor analysis. When there were two peaks the analysis was by normal approximation to Poisson distribution. In younger men (under 45 years) admitted to hospital there was a dominant spring peak and an autumn trough. A bimodal pattern of spring and winter peaks was evident for hospital admissions in older male age groups: with increasing age the spring peak diminished and the winter peak increased. In contrast, female hospital admissions showed a dominant winter/summer pattern of seasonal variation. In male and female CHD deaths seasonal variation showed a dominant pattern of winter peaks and summer troughs, with the winter peak spreading into spring in the two youngest male age groups. CHD incidence in women showed a winter/summer rhythm, but in men the spring peak was dominant up to the age of 55. The male, age related spring peak in CHD hospital admissions suggests there is an androgenic risk factor for myocardial infarction operating through an unknown effector mechanism. As age advances and reproduction becomes less important, the well defined winter/summer pattern of seasonal variation of CHD is superimposed, and shows a close relationship with the environment, especially temperature, or the autumn and early winter fall in temperature.

Role of nutrition in the prevention and treatment of coronary heart disease in women

Coronary heart disease (CHD) is the major cause of death in women. Because the manifestation of CHD differs in women and men (men are more likely to have acute CHD and women are more likely to have chronic CHD), it is imperative to explore the unique aspects of CHD in women. In addition, there is a critical need to increase our understanding of the effect of CHD risk factor modification on coronary morbidity and mortality in women. Several major CHD risk factors in women, such as elevated blood lipids and lipoproteins, body weight, and, frequently, hypertension, are beneficially responsive to nutrition intervention. Approximately 27% of all women and 50% of women aged 55 to 74 years are candidates for dietary intervention. The fact that women respond positively to dietary intervention has been well established by researchers. Studies are needed to determine the efficacy of risk factor modification achieved by dietary and other hygienic approaches as well as by other more rigorous therapies (eg, drugs and surgery) on the primary and secondary prevention of CHD in women. Finally, it will be important to understand the effects of gender, menopausal status, and age on dietary responsiveness. We must gain a better understanding of these issues so that we may significantly reduce the incidence of CHD in women.

Sex, plasma lipoproteins, and atherosclerosis: Prevailing assumptions and outstanding questions

We review the hypothesis that the incidence of coronary heart disease (CHD) is higher in men than in women due to differences in plasma lipoprotein risk factors between the sexes. Men and women appear to be equally susceptible to the effects of lipoprotein risk factors for CHD, and the difference between the sexes in lipoprotein risk factors for CHD appears to be consistent with their being, at least in part, responsible for the sex difference in CHD. This is apparent both when men and women of equal age are compared, and when age-related variations in the sex differences in plasma lipoproteins and CHD are considered. Differences between the sexes in lipoprotein concentrations are still present when sex differences in adiposity, cigarette smoking, physical activity, and diet are taken into account. Evidence relating these sex differences in CHD and lipoproteins to the effects of sex hormones is critically examined. It is commonly accepted that androgens induce changes in lipoprotein concentrations that would predispose towards CHD, whereas estrogens are held to have opposite effects. However, much of the evidence for this comes from studies of changes associated with administration of synthetic gonadal steroids or with changes in gonadal function. Studies of differences in lipoprotein metabolism in normal men and women are extremely limited. In males high-density lipoprotein (HDL) cholesterol levels fall at puberty, correlating with the rise in plasma testosterone concentrations. In females, HDL levels do not change at puberty, despite the rise in estrogen concentrations. Evidence for lipoprotein changes during the menopause, when estrogen levels decline, is equivocal. Similarly, the evidence for an increase in CHD incidence at the menopause is inconclusive. National mortality data indicate that the decreasing sex difference in CHD after 50 years of age is due to a declining rate of increase in men rather than to an acceleration in CHD incidence in women. In men the age-related increase in low-density lipoprotein (LDL) concentrations diminishes beyond 50 years of age, whereas in women the rate of increase remains unchanged. Studies of the effects of gonadectomy are of doubtful relevance in assessing the roles of sex hormones in CHD, and have not been performed with sufficient rigor to provide definitive conclusions. The effects of exogenously administered androgens and estrogens on lipoprotein concentrations have dominated the evaluation of the hypothesis that differences in sex hormones underlie the sex difference in lipoprotein concentrations and hence CHD incidence. However, these studies have been confounded by the variety and nature of gonadal steroids employed, with native (nonsynthetic) hormones being poorly represented. The lack of thorough prospective studies of risk factors for CHD in women, comparative studies of lipoprotein metabolism in healthy men and women, and prospective studies relating endogenous sex hormone levels, plasma lipoprotein concentrations, and development of CHD all remain serious omissions in our understanding of the pathogenesis of the major cause of death in Western society.