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Sex, plasma lipoproteins, and atherosclerosis: Prevailing assumptions and outstanding questions
Abstract
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.(ABSTRACT TRUNCATED AT 400 WORDS)
... Tous les résultats scientifiques ne vont cependant pas dans ce sens. L'écart d'incidence des cardiopathies ischémiques entre les hommes et les femmes a tendance à se réduire avec l'âge, mais cette convergence des courbes d'incidence dans les hautes tranches d'âge pourrait plus être liée à une inflexion de la courbe d'incidence chez les hommes qu'à une accélération de l'incidence chez les femmes après la ménopause 62 . ...
... Par ailleurs, le fait que le niveau du cholestérol HDL soit plus élevé chez la femme que chez l'homme à l'âge adulte, ce qui doit contribuer au "retard" de survenue de la maladie chez la femme par rapport à l'homme, semble plus un effet androgénique qu'estrogénique 63 . En effet, jusqu'à la puberté, les niveaux de cholestérol HDL chez les filles et chez les garçons sont comparables, et c'est à la puberté, parallèlement à l'augmentation des taux circulants de testostérone, que le niveau de cholestérol HDL baisse chez les garçons tandis qu'il reste inchangé chez les filles, malgré l'augmentation de la production d'estrogènes [62][63][64][65] . ...
... However, female animals on the HFS diet also experienced an increase in HDL cholesterol levels where males did not. It has been well established in previous literature that estrogen is associated with an increase in HDL cholesterol 40 . Exposure to the HFS diet also resulted in various effects of both diet and sex on intramuscular fat infiltration, fibrosis, and macrophage invasion in the VL and soleus muscles. ...
Metabolic abnormalities associated with excess adiposity in obesity contribute to many noncommunicable diseases, including sarcopenic obesity. Sarcopenic obesity is the loss of muscle mass coupled with excess fat mass and fatty infiltrations in muscle tissue called myosteatosis. A diet-induced obesity model was developed to study fat infiltration in muscle tissue. Only male rats have been considered in these investigations neglecting that female rats might respond differently. The objective of this study was to determine if the response to diet-induced obesity can be generalized to both sexes, or whether sex affects the response to the HFS diet, as indicated by markers of metabolic syndrome and changed in muscle integrity. Using a combination of histological staining techniques, quantitative proteomics, and measures of metabolic syndrome and inflammation, it was determined that the diet-induced obesity model in female Sprague-Dawley rats is a viable model with pronounced effects on the musculoskeletal system. We found sex-dependent and muscle-specific differences in intramuscular fat infiltration between male and female rats receiving the obesogenic diet. Including females in research may allow for identifying distinct causes of the mechanistic relationship between diet, obesity, metabolic syndrome, and the sex-dependent differential effects of these factors on adaptation and degeneration of musculoskeletal tissues.
... The association between RC and risk of AF remained statistically significant for men, possibly because of their higher AF incidence and lower serum TC and triglyceride levels with age than women. 50,51 Moreover, the electrophysiological properties of the atria differ between men and women. 52 The association between RC and AF risk was not statistically significant among participants with a history of diabetes. ...
Background
Evidence for the relationship between remnant cholesterol (RC) and incident atrial fibrillation (AF) risk remains sparse and limited.
Methods and Results
Participants were enrolled between 2006 and 2010 and followed up to 2021. The multivariable Cox proportional hazards model was used to examine the relationship between RC quartiles and risk of incident AF. Subgroup analyses and sensitivity analyses were performed to explore the potential modification of the association and the robustness of the main findings. A total of 422 316 participants (mean age, 56 years; 54% women) were included for analyses. During a median follow‐up of 11.9 years (first quartile–third quartile, 11.6–13.2 years), there were 24 774 AF events documented with an incidence of 4.92 events per 1000 person‐years (95% CI, 4.86–4.98). Participants in higher RC quartiles had a lower risk of incident AF than those in the lowest quartile (first quartile): hazard ratio (HR)=0.96 (95% CI, 0.91–1.00) for second quartile; HR=0.92 (95% CI, 0.88–0.96) for third quartile; and HR=0.85 (95% CI, 0.81–0.89) for fourth quartile ( P for trend <0.001). The association between RC quartiles and risk of incident AF was stronger in participants aged ≥65 years, in men, and in participants without history of diabetes when compared with control groups ( P <0.001 for interaction).
Conclusions
On the basis of data from this large‐scale prospective cohort study, elevated RC was associated with a lower risk of incident AF.
... The only gender differences that remained in this sample were in HDL-C (favoring women) and resting heart rate (favoring men). These findings suggest that gender differences in these two variables may be due to factors other than the known influence of age and body mass (e.g., sex differences in lipid metabolism; see Godsland, Wynn, Path, Crook, & Miller, 1987). ...
This study reports on standard coronary risk factors (plasma lipids and lipoproteins, blood pressure, heart rate, age, body mass index) and psychosocial variables (job strain, Type A behavior, hostility, illnesses, medical and psychological symptoms, health-damaging behavior) in a community sample of 324 employed men, 203 employed women, and 155 female homemakers. Employed women reported less hostility and fewer illnesses than homemakers and had lower cholesterol levels than homemakers and men. Job characteristics were unrelated to standard coronary risk factor levels in both sexes, but predicted medical symptoms and health-damaging behavior in men. These findings suggest that employment is associated with enhanced medical and physical well-being among women and point to possible behavioral and psychological pathways by which job strain may adversely influence men's health.
... Accordingly, the number of abnormal lipid profiles was greater in men than in women, and the prevalence of high LDL-C, low HDL-C, and high triglyceride levels was higher in men than in women. In women, cholesterol levels rise after menopause and exceed those of men 25) . In this study, we focused on young people and included incidence of MI, AP, and HF increased with the number of abnormal lipid profiles in both men and women, whereas the incidence of stroke increased with the number of abnormal lipid profiles only in men but not in women. ...
Aim: Using a nationwide epidemiological database, we sought to examine whether there was a sex difference in the association between lipid profiles and subsequent cardiovascular disease (CVD) in young adults.
Methods: Medical records of 1,909,362 young adults (20–49 years old) without a prior history of CVD and not taking lipid-lowering medications were extracted. We conducted multivariable Cox regression analyses to identify the association between the number of abnormal lipid profiles and incident CVD.
Results: After a mean follow-up of 3.4±2.6 years, myocardial infarction (MI), angina pectoris (AP), stroke, and heart failure (HF) developed in 2,575 (0.1%), 26,006 (1.4%), 10,748 (0.6%), and 24,875 (1.3%) subjects, respectively. The incidence of MI, AP, and HF increased with the number of abnormal lipid profiles in both men and women, whereas the incidence of stroke increased with the number of abnormal lipid profiles only in men but not in women. Multivariable adjusted hazard ratios (HRs) for MI per 1-point higher abnormal lipid profile were 1.57 (95% confidence interval [CI] 1.49–1.65) in men and 1.25 (95% CI 1.07–1.47) in women. HRs for AP, stroke, and HF per 1-point higher abnormal lipid profile were 1.14 (95% CI 1.12–1.16), 1.06 (95% CI 1.02–1.09), and 1.10 (95% CI 1.08–1.12) in men and 1.18 (95% CI 1.13–1.23), 1.09 (95% CI 1.03–1.16), and 1.10 (95% CI 1.05–1.14) in women.
Conclusion: Our analysis demonstrated an association between the number of abnormal lipid profiles and incident CVD in both men and women. The association between the number of abnormal lipid profiles and incident MI was pronounced in men.
... Ethinyl estradiol raises HDL cholesterol levels (Jacobs et al 1990). Conversely, progestins can lower HDL cholesterol levels (Kay , 1982, Godsland et al 1987, Wahl et al 1983, Bradley et al 1978 by increasing hepatic lipase activity (Krauss et al 1983 females between the ages of 20 and 50 years, females who gave their written consent and females without predisposing factors or conditions to CV disease prior to contraceptive use. Data and blood sample collection A questionnaire was administered to obtain basic information on age, duration of drug use, contraceptive type, etc. Blood samples were collected by venepuncture from each subjects at baseline (0 Months), 3 months, 6 months, 9 months and 12 months respectively. ...
... We observed notable sex differences in lipoprotein profiles in this study, findings which have also been reported in previous research [13]. In particular, it has been observed that as women age, post-menopausal total cholesterol and LDL cholesterol concentrations surpass those in men [61]. Nevertheless, although women experience an escalation in the incidence of CVD after menopause, they continue to have significantly lower CVD morbidity and mortality relative to age-matched men [62]. ...
Background and objectives
Lipoprotein particle concentrations and size are associated with increased risk for atherosclerosis and premature cardiovascular disease. Studies also suggest that certain dietary behaviours may be cardioprotective. Limited comparative data regarding any dietary score/index-lipoprotein particle subclass associations exist. Thus, our objective was to assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Health Eating Index-2015 (HEI-2015), Mediterranean Diet (MD) and Energy-adjusted Dietary Inflammatory Index (E-DII™) scores and plasma lipids and lipoprotein profiles to test the hypothesis that healthier diet (better quality and more anti-inflammatory) would be associated with a more favourable lipoprotein profile.
Materials and methods
This was a cross-sectional study of 1862 men and women aged 46–73 years, randomly selected from a large primary care centre in Ireland. DASH, HEI-2015, MD and E-DII scores were derived from food frequency questionnaires. Lipoprotein subclass particle concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with lipoprotein particle subclasses.
Results
In fully adjusted models, higher diet quality or a more anti-inflammatory diet was associated with less large and medium very low-density lipoprotein (VLDL) (DASH and HEI-2015), intermediate-density lipoprotein (IDL) (DASH, MD and E-DII) and small high-density lipoprotein (HDL) (DASH, HEI-2015 and E-DII) particles. After accounting for multiple testing, relationships with large VLDL (DASH: β = -0.102, p = .037), IDL (DASH: β = -0.089, p = .037) and small HDL (DASH: β = -0.551, p = .014 and E-DII: β = 0.483, p = .019) concentrations persisted.
Conclusions
These findings provide evidence that better diet quality, determined by the DASH score, may be more closely associated with a more favourable lipoprotein particle subclass profile in middle-to older-aged adults than the HEI-2015, MD and E-DII scores. A less pro-atherogenic lipoprotein status may be a potential mechanism underlying the cardioprotective effects of higher dietary quality.
... Similarly, female sex was associated with a statistically significant reduction in fasting triglycerides, whereas male sex was associated with a statistically significant increase in fasting triglycerides. Differences by sex in glucose homeostasis and lipoproteins have been described previously (71,72). It is therefore possible that changes in these outcomes are also influenced by sex. ...
Despite the publication of several of meta-analyses in recent years, the effects of fructose on human health remains a topic of debate. We previously undertook two meta-analyses on post-prandial and chronic responses to isoenergetic replacement of fructose for sucrose or glucose in food or beverages (Evans et al. 2017, AJCN 106:506–518 & 519–529). Here we report on the results of an updated search with a complete re-extraction of previously identified studies and a new and more detailed subgroup-analysis and meta-regression. We identified two studies that were published after our previous analyses, which slightly altered effect sizes and conclusions. Overall, the isoenergetic substitution of fructose for glucose resulted in a statistically significant but clinically irrelevant reduction in fasting blood glucose, insulin, and triglyceride concentrations. A subgroup analysis by diabetes status revealed much larger reductions in fasting blood glucose in people with impaired glucose tolerance and type 2 diabetes. However, each of these subgroups contained only a single study. In people with a healthy body mass index, fructose consumption was associated with statistically significant, but clinically irrelevant reductions in fasting blood glucose and fasting blood insulin. Meta-regression of the outcomes by a number of pre-identified and post-hoc covariates revealed some sources of heterogeneity, such as year of publication, age of the participants at baseline, and participants' sex. However, the small number of studies and the large number of potential covariates precluded detailed investigations of effect sizes in different subpopulations. For example, well-controlled, high quality studies in people with impaired glucose tolerance and type 2 diabetes are still lacking. Taken together, the available data suggest that chronic consumption of fructose is neither more beneficial, nor more harmful than equivalent doses of sucrose or glucose for glycemic and other metabolic outcomes.
... Swiger et al. 9 earlier hypothesized that the average lipid profile of women undergoes unfavorable changes compared with men after midlife. Godsland et al. 10 opined that as women age, the serum concentrations of triglycerides, low-density lipoprotein cholesterol and Total Cholesterol (TC) surpass those in men. Menopause itself is associated with an increased prevalence of dyslipidemia but not hypertension or insulin resistance, independent of the effect of chronological aging. ...
Owing to its high prevalence, dyslipidemia is rapidly becoming a major public heart issue worldwide, and especially in Nigeria. Although it is a preventable significant risk factor for coronary heart disease, it is a common leading cause of death in Nigeria. The study therefore investigated the lipid profiles of patients attending Metabolic Clinic at the Delta State University Teaching Hospital (DELSUTH). A total of 713 participants were recruited for the study. Blood samples (5mls) were collected via venipuncture from each of the participants and distributed into tubes containing EDTA and fluoride oxalate. A spectrophotometer was used to conduct the lipid analysis, and the normal operating assay protocol was followed. Results showed total cholesterol in the male (194.6 mg/dL) were generally lower than in the females, particularly for participants below the age of 40. However, as the ages progressed (that is, above 40 years), total cholesterol in males became higher than those in the females. Antherogenic ratio as well as antherogenic index of plasma were higher in the female gender at ages below 40 years. The study showed that the risk of hypercholesterolemia may be higher within the active age period of 30-60 years. As seen in the current study, plasma lipid levels change drastically by sexual development or maturity, and the trends vary by age and sex. The study also significantly demonstrated the elevated lipids levels in younger women in the study population than older men. When assessing screening and diagnostic criteria for classifying individuals with elevated blood lipid levels, pubertal or sexual growth may be taken into account.
... 138 High cholesterol levels were shown to be one of the most critical risk factors for the development of atherosclerosis. 231 Many types of research have examined the correlation between levels of T and lipoprotein profile. However, extensiveprospective population-based studies linking between T and lipid levels are not available. ...
Introduction
Cardiometabolic syndrome (CMS), as a bunch of metabolic disorders mainly characterized by type 2 diabetes mellitus (T2DM), hypertension, atherosclerosis, central adiposity, and abdominal obesity triggering androgen deficiency, is one of the most critical threats to men. Although many significant preclinical and clinical findings explain CMS, new approaches toward common pathophysiological mechanisms and reasonable therapeutic targets are lacking.
Aim
To gain a further understanding of the role of androgen levels in various facets of CMS such as the constellation of cardiometabolic risk factors including central adiposity, dyslipidemia, insulin resistance, diabetes, and arterial hypertension and to define future directions for development of effective therapeutic modalities.
Methods
Clinical and experimental data were searched through scientific literature databases (PubMed) from 2009 to October 2019.
Main Outcome Measure
Evidence from basic and clinical research was gathered with regard to the causal impact and therapeutic roles of androgens on CMS.
Results
There are important mechanisms implicated in androgen levels and the risk of CMS. Low testosterone levels have many signs and symptoms on cardiometabolic and glycometabolic risks as well as abdominal obesity in men.
Clinical Implications
The implications of the findings can shed light on future improvements in androgen levels and add potentially predictive risk for CMS, as well as T2DM, abdominal obesity to guide clinical management in the early stage.
Strengths & Limitations
This comprehensive review refers to the association between androgens and cardiovascular health. A limitation of this study is the lack of large, prospective population-based studies that analyze the effects of testosterone treatment on CMS or mortality.
Conclusion
Low testosterone levels have several common features with metabolic syndrome. Thus, testosterone may have preventive role in the progress of metabolic syndrome and subsequent T2DM, abdominal obesity, and cardiovascular disease and likely affect aging men's health mainly through endocrine and vascular mechanisms. Further studies are necessary to evaluate the therapeutic interventions directed at preventing CMS in men.
Kirlangic OF, Yilmaz-Oral D, Kaya-Sezginer E, et al. The Effects of Androgens on Cardiometabolic Syndrome: Current Therapeutic Concepts. Sex Med 2020;XX:XXX–XXX.
... In previously published studies, differences in atherogenic profile, in terms of both gender and menopausal status, were suggested. [24][25][26][27] Gupta et al. developed a hospital database, which included 67,395 subjects, and observed greater hypercholesterolemia and lower HDL-C in women. A lower decline was observed in women. ...
Aim:
To understand age- and gender-related differences and secular trends in coronary artery disease (CAD) lipid profiles and the characteristic of dyslipidemia in western China.
Methods:
An age-matched case-control study, including 2400 patients and 1200 controls was performed. All blood lipid tests evaluated from January 2012 to January 2015 at First Affiliated Hospital of Xinjiang Medical University were analyzed. Details of the gender and age of the patients were available. Trends were calculated using linear regression and Mantel-Haenszel X2 analyses.
Results:
We determined the associations among total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (apoA-1), apolipoprotein B (apoB), nonhigh-density lipoprotein cholesterol (non-HDL-C), and high-density lipoprotein cholesterol (HDL-C) with CAD for different ages and gender. Except for patients who were <40 years old, the plasma levels of TC, TG, LDL-C, non-HDL-C, apoB, and apoB/apoA-1 were higher in the cases than in controls, and the average levels of these markers decreased significantly as age increased. In contrast, the levels of apoA-1 and HDL-C were significantly higher in the controls than in the patients, and the levels of these markers significantly increased as age increased. Women had higher levels of TC, LDL-C, non-HDL-C, and apoB and a higher value of the apoB/apoA-1 ratio compared to men. The decrease in the average levels of these markers with age was significantly lower in women compared to men. Logistic regression was used to compute the odds ratio of CAD for a one standard deviation change in each lipid marker. Most notably, the apoB/apoA-1 ratio could be a strong risk factor for CAD, and increasing values of the ratio showed a curved line for the graph of the relationship between the ratio and risk.
Conclusions:
Our results confirmed that serum lipid levels in patients with CAD varied by age and gender. The apoB/apoA-1 ratio remains a strong risk factor for CAD.
... All rights reserved. cholesterol levels in women and men showed opposite directions of association with glycaemia such that, with increasing glycaemia, they converged and the well-established advantage of high HDL cholesterol levels in women 30 was eliminated. In the Thai women we studied, HDL cholesterol levels fell with increasing HbA1c, which accords with previously-reported observations of the relationship between glycaemia and HDL cholesterol across the full range of glycaemia; ...
Background
Relationships between cardiometabolic risk and glycaemia have been rarely studied in people under clinical evaluation and treatment for cardiometabolic risk and with prediabetes. We investigated relationships between glycaemia and cardiometabolic risk factors in clinic participants with prediabetes.
Methods
This was a cross‐sectional analysis of data collected at a centre in Thailand. Clinic attendees were at high‐risk of diabetes or cardiovascular disease, with HbA1c 39‐<48 mmol/mol or fasting plasma glucose (FPG) 5.6‐<7.0 mmol/L. The relationships between glycaemia and cardiometabolic risk factors were explored.
Results
Of 357 participants, two or more insulin resistance‐related metabolic disturbances were present in 84%; 61% took a statin and 75% an antihypertensive agent. Independently of age, gender, adiposity, medication use, possible NAFLD and gender‐glycaemia interaction, neither FPG nor HbA1c were associated with variation in any other cardiometabolic risk factors. HDL cholesterol decreased with HbA1c in women (female*HbA1c interaction, p=0.03) but, unexpectedly, increased with FPG in men (male*FPG interaction, p=0.02).
Conclusion
Overall, in Thai people treated for high‐cardiometabolic risk and with prediabetes defined by FPG and/or HbA1c, neither FPG nor HbA1c were associated with other cardiometabolic risk factors. However, according to gender, HDL cholesterol showed the expected relationship with glycaemia in women but the reverse in men.
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... The decrease in HDL levels is conserved among HIV-1infected individuals, independently of their CRP levels ( Figure 1D). As previously reported (44), women showed higher HDL levels than men, but only within the healthy control group (data no shown). In addition, alterations in HDL levels were no affected by normal or overweight conditions of patients (data no shown). ...
Introduction
High-density lipoproteins (HDL) are responsible for the efflux and transport of cholesterol from peripheral tissues to the liver. In addition, HDL can modulate various immunological mechanisms, including the inflammatory response. Inflammasomes are multiprotein complexes that have been reported to be activated during human immunodeficiency virus type 1 (HIV-1) infection, thus contributing to immune hyperactivation, which is the main pathogenic mechanism of HIV-1 progression. However, the relationship between HDL and inflammasomes in the context of HIV-1 infection is unclear. Therefore, this research aims to explore the association between HDL and the components of the inflammatory response during HIV-1 infection.
Methodology
A cross-sectional study, including 36 HIV-1-infected individuals without antiretroviral treatment and 36 healthy controls matched by sex and age, was conducted. Viral load, CD4+ T-cell counts, serum HDL, and C-reactive protein (CRP) were quantified. Serum cytokine levels, including IL-1β, IL-6, and IL-18, were assessed by ELISA. The inflammasome-related genes in peripheral blood mononuclear cells were determined by quantitative real-time PCR.
Results
HIV-1-infected individuals showed a significant decrease in HDL levels, particularly those subjects with higher viral load and lower CD4+ T-cell counts. Moreover, upregulation of inflammasome-related genes (NLRP3, AIM2, ASC, IL-1β, and IL-18) was observed, notably in those HIV-1-infected individuals with higher viral loads (above 5,000 copies/mL). Serum levels of IL-6 and CRP were also elevated in HIV-1-infected individuals. Significant negative correlations between HDL and the mRNA of NLRP3, AIM2, ASC, IL-1β, and IL-18, as well as viral load and CRP were observed in HIV-1-infected individuals. Likewise, a significant positive correlation between HDL and CD4+ T-cell counts was found.
Conclusion
In summary, our results indicate that HDL might modulate the expression of several key components of the inflammasomes during HIV-1 infection, suggesting a novel role of HDL in modifying the inflammatory state and consequently, the progression of HIV-1 infection.
... [15,16] Ethinyl estradiol raises HDL cholesterol levels conversely progestin can lower HDL cholesterol levels by increasing hepatic lipase activity. [17][18][19][20] Generally combination drugs lowered HDL2 levels and increased HDL3 levels In group A a significant fall is seen in HDL level. This finding correlates well with observation of Aurell and Crammer (1966) who observed significant fall in HDL level with high dose estrogen pills. ...
... Previous studies reported conflicting results regarding cardiovascular risk in persons using smokeless tobacco. Case-control studies suggest no increased risk of myocardial infarction or stroke in regular snuff users 11,12, but a tendency towards increased risk of fatal myocardial infarction 12 Women are generally considered less vulnerable to CAD because of the protection by sex hormones 45,46 47 in their study they found diabetes (20%), dyslipidemia (49%), and hypertension (55%). Despite this prevalent coronary risk factor load, only 174 (29%) of these women had angiographic CAD. ...
Background: Tobacco use is associated with numerous illnesses and incidence, use patterns, and correlates of smokeless tobacco have become increasingly important as usage rates rise and harmful health effects become established.
Method: Total 312 consecutive female non-smoker patients who underwent diagnostic coronary angiography were included in the study. Detail history of their smokeless tobacco use habit and exposure to second hand smoking in home were obtained by using a questionnaire. Patients were divided into four groups according to history of use of SLT or exposure to SHS. Group I: non-user of SLT and non-exposed to SHS; Group II: exposed to SHS only; Group III: user of SLT only and Group IV: user of SLT and exposed to SHS. The proportion of patients with positive angiogram for CAD was compared among the groups.
Results: Mean±SD of age of the respondents was 49.9±9.9 years. Among the patients 114(36.5%) were non exposed of SLT or SHS, 71(22.8%) were Exposed to SHS only, 73(23.4%) were user of SLT only and 54(17.3%) were exposed to SHS and user of SLT. Among the patients 224(69.8%) were hypertensive, 118 (37.8%) were diabetic and 36(11.5%) were dyslipidaemic. Coronary angiogram was positive in 138(44.2%). Among 138 the patients with CAD, non exposed of SLT or SHS, exposed to SHS only, user of SLT only and exposed to SHS and User of SLT were 45(32.6%), 28(20.3%), 38(27.5%) and 27(19.6%) respectively. The multiple logistic regressions for risk factor of CAD positive showed that age >50 years are 2.226 times higher risk to developed CAD than age ≤50 years. Hypertensive patients had 2.136 times higher risk developing CAD and diabetic patients had 1.733 times higher risk of developing CAD. Among the patients exposed to SHS only, user of SLT
only and both exposed to SHS and user of SLT were 1.271, 1.514 and 1.501 times more risk to develop CAD than not exposed to SHS and not user of SLT.
Conclusion: Although the relationship is statistically non significant, the result indicates that the exposure to SHS have additive effect on the relationship of SLT use with CAD in women. Further large scale studies need to be taken to clarify the relationships.
Key wards: Smokeless Tobacco (SLT); Second Hand Smoke (SHS); Coronary Artery Disease (CAD)
... Another study shows the same and prosperous result in animal model. This discovery was con rmed in animal models as well (Godsland et al., 1987). ...
The objective of this study was to assess the testosterone role in modification of ischemic heart disease. All subjects were male aged between 30 to 80 years. At the start of study, blood pressure, serum testosterone, lipid profile and left ventricular function were recorded. Males who were at high risk of cardiovascular disease have low endogenous testosterone level. The testosterone therapy, 250mg/2mlweekly (Intramuscularly) for six months was sufficient to lower the risk of further cardiac complications by decreasing serum total cholesterol, low density lipoprotein and triglycerides levels (p<0.0001) and showed improvement in high density lipoprotein and serum testosterone levels (p<0.02). Moreover it has also ameliorated the Left Ventricular Function. The study concluded that exogenous testosterone may be considered a valuable addition as a regular therapy in Ischemic Heart Disease patients in order to codify their cardiac functions.
... Another study shows the same and prosperous result in animal model. This discovery was con rmed in animal models as well (Godsland et al., 1987). ...
The objective of this study was to assess the testosterone role in modification of ischemic heart
disease. All subjects were male aged between 30 to 80 years. At the start of study, blood pressure,
serum testosterone, lipid profile and left ventricular function were recorded. Males who were at high
risk of cardiovascular disease have low endogenous testosterone level. The testosterone therapy,
250mg/2mlweekly (Intramuscularly) for six months was sufficient to lower the risk of further cardiac
complications by decreasing serum total cholesterol, low density lipoprotein and triglycerides levels
(p<0.0001) and showed improvement in high density lipoprotein and serum testosterone levels
(p<0.02). Moreover it has also ameliorated the Left Ventricular Function. The study concluded that
exogenous testosterone may be considered a valuable addition as a regular therapy in Ischemic Heart
Disease patients in order to codify their cardiac functions.
Key words: Ischemic Heart Disease, Testosterone, HDL, LDL
... Another study shows the same and prosperous result in animal model. This discovery was con rmed in animal models as well(Godsland et al., 1987). The impact of exogenous testosterone administration is helpful in maintaining the levels of serum testosterone levels in men with IHD. ...
The objective of this study was to assess the testosterone role in modification of ischemic heart disease. All subjects were male aged between 30 to 80 years. At the start of study, blood pressure, serum testosterone, lipid profile and left ventricular function were recorded. Males who were at high risk of cardiovascular disease have low endogenous testosterone level. The testosterone therapy, 250mg/2mlweekly (Intramuscularly) for six months was sufficient to lower the risk of further cardiac complications by decreasing serum total cholesterol, low density lipoprotein and triglycerides levels (p<0.0001) and showed improvement in high density lipoprotein and serum testosterone levels (p<0.02). Moreover it has also ameliorated the Left Ventricular Function. The study concluded that exogenous testosterone may be considered a valuable addition as a regular therapy in Ischemic Heart Disease patients in order to codify their cardiac functions.
... Previous studies reported conflicting results regarding cardiovascular risk in persons using smokeless tobacco. Case-control studies suggest no increased risk of myocardial infarction or stroke in regular snuff users 11,12, but a tendency towards increased risk of fatal myocardial infarction 12 Women are generally considered less vulnerable to CAD because of the protection by sex hormones 45,46 47 in their study they found diabetes (20%), dyslipidemia (49%), and hypertension (55%). Despite this prevalent coronary risk factor load, only 174 (29%) of these women had angiographic CAD. ...
... Obesity may also exaggerate unfavorable lipid profiles in aging and menopausal women. Some studies have reported a more frequent age-related increase in the prevalence of being overweight or obese [7,22] in females than in males [23] In addition, studies have reported a greater increase in fat mass and waist circumference or abdominal skinfold thickness in postmenopausal compared to premenopausal women [23][24][25] An increase in abdominal lipoprotein lipase activity is observed after the withdrawal of estrogens, which leads to the local elevation of free fatty acids and the accumulation of abdominal fat [26,27]. Our data showed that higher mean number of daily working hours was associated with higher BMI and PBF. ...
Background
Previous studies have identified a link between gender and the various risk factors associated with obesity. We examined obesity risk factors in working adults to identify the effects of differences in body mass index (BMI) and percentage body fat (PBF) between women and men. MethodsA total of 1,120 adults agreed to participate in the study. Data from 711 participants, including 411 women and 300 men, were analyzed. Multiple logistic regression analysis was used to estimate the effects of risk factors on obesity and being overweight. In addition, the least-squares (LS) means of both BMI and PBF were estimated by analysis of covariance (ANCOVA) in a generalized linear model. ResultsIncreases in BMI and PBF were significantly related to an age > 50 years and long working hours in women after compensating for confounding factors. Using the PBF criterion, the odds ratio (OR) of being overweight or obese in women > 50 years of age who worked for > 9 h a day was 3.9 (95% confidence interval [CI], 1.05–11.00). For BMI, women who were > 50 years of age and worked for > 9 h a day were 3.82 times (95% CI, 1.31–11.14) more likely to be overweight or obese than those who were < 50 years of age and worked for < 9 h a day. Conclusion
Obesity in working adults was associated with > 50 years of age and long working hours in women. Further studies are needed to investigate the underlying mechanisms of this relationship and its potential implications for the prevention and management of excess weight and obesity.
... Another study shows the same and prosperous result in animal model. This discovery was con rmed in animal models as well(Godsland et al., 1987). The impact of exogenous testosterone administration is helpful in maintaining the levels of serum testosterone levels in men with IHD. ...
The objective of this study was to assess the testosterone role in modification of ischemic heart
disease. All subjects were male aged between 30 to 80 years. At the start of study, blood pressure,
serum testosterone, lipid profile and left ventricular function were recorded. Males who were at high
risk of cardiovascular disease have low endogenous testosterone level. The testosterone therapy,
250mg/2mlweekly (Intramuscularly) for six months was sufficient to lower the risk of further cardiac
complications by decreasing serum total cholesterol, low density lipoprotein and triglycerides levels
(p<0.0001) and showed improvement in high density lipoprotein and serum testosterone levels
(p<0.02). Moreover it has also ameliorated the Left Ventricular Function. The study concluded that
exogenous testosterone may be considered a valuable addition as a regular therapy in Ischemic Heart
Disease patients in order to codify their cardiac functions.
... In line with previous literatures, our results showed higher HDL-C and lower TG level in women, 36 and lower leptin level in men. 37,38 These findings confirmed that sex can have a role as a confounder and therefore all the analyses in the present study were performed with controlling for sex effect as well. ...
Objectives:
C-reactive protein (CRP) has been shown to correlate with health-related quality of life (HRQL) in some chronic medical conditions. However, these associations have not yet described in spinal cord injury (SCI). In this study, we tried to identify biomarkers associated with HRQL in SCI.
Design:
Cross-sectional.
Setting:
Tertiary rehabilitation center.
Participants:
Referred patients to Brain and Spinal Cord Injury Research Center between November 2010 and April 2013.
Outcome measure:
Blood samples were taken to measure circulatory CRP, leptin, adiponectin, ferritin, parathyroid hormone, calcitonin, thyroid hormones, fasting plasma glucose and lipid profile. All the analyses were performed with adjustment for injury-related confounders (level of injury, injury completeness and time since injury) and demographic characteristics. HRQL was measured with Short Form health survey (SF-36).
Results:
The initial inverse association between CRP and total score of SF-36 (P: 0.006, r = -0.28) was lost after adjustment for confounders. However, the negative correlation between CRP and Mental Component Summary (MCS) remained significant (P: 0.0005, r = -0.38). Leptin level was inversely correlated with Physical Component Summary (PCS) (P: 0.02, r = -0.30).
Conclusion:
Although CRP and leptin levels were not related with total scores of SF-36 questionnaire, CRP can be more useful in determining mental component of HRQL whereas leptin can be a determinant of physical component. The combined consideration of these two biomarkers may help to predict HRQL in individuals with SCI.
... In line with previous literatures, our results showed higher HDL-C and lower TG level in women, 36 and lower leptin level in men. 37,38 These findings confirmed that sex can have a role as a confounder and therefore all the analyses in the present study were performed with controlling for sex effect as well. ...
Objectives: C-reactive protein (CRP) has been shown to correlate with health-related quality of life (HRQL) in
some chronic medical conditions. However, these associations have not yet described in spinal cord injury
(SCI). In this study, we tried to identify biomarkers associated with HRQL in SCI.
Design: Cross-sectional.
Setting: Tertiary rehabilitation center.
Participants: Referred patients to Brain and Spinal Cord Injury Research Center between November 2010 and
April 2013.
Outcome Measure: Blood samples were taken to measure circulatory CRP, leptin, adiponectin, ferritin,
parathyroid hormone, calcitonin, thyroid hormones, fasting plasma glucose and lipid profile. All the analyses
were performed with adjustment for injury-related confounders (level of injury, injury completeness and time
since injury) and demographic characteristics. HRQL was measured with Short Form health survey (SF-36).
Results: The initial inverse association between CRP and total score of SF-36 (P: 0.006, r = −0.28) was lost after
adjustment for confounders. However, the negative correlation between CRP and Mental Component Summary
(MCS) remained significant (P: 0.0005, r = −0.38). Leptin level was inversely correlated with Physical
Component Summary (PCS) (P: 0.02, r = −0.30).
Conclusion: Although CRP and leptin levels were not related with total scores of SF-36 questionnaire, CRP can
be more useful in determining mental component of HRQL whereas leptin can be a determinant of physical
component. The combined consideration of these two biomarkers may help to predict HRQL in individuals
with SCI.
Keywords: Quality of Life, Spinal cord injury, Health survey, Leptin, C reactive protein
Menopause may influence negatively the cardiovascular system of women, especially that of smokers. The aim of
our study was to compare lipid levels and left ventricular function in postmenopausal women smokers and non-smokers
during 12 months of oral estrogen replacement therapy. The study group included healthy postmenopausal women, 30
smokers and 32 non-smokers. Before and in 6 month intervals the following parameters were followed: total cholesterol,
LDL-, HDL-cholesterol, triglycerides, blood pressure and echocardiographic parameters of systolic and diastolic left
ventricular function. Before therapy non-smokers had higher total and LDL-cholesterol, when compared to smokers. Oral
estrogen replacement therapy significantly decreased levels of total and LDL-cholesterol and increased HDL-cholesterol,
only in non-smokers. No change in lipid levels was observed in smokers. However, women who smoked longer had higher
triglyceride levels after 12 months of oral estrogen replacement therapy. Echocardiography revealed significant improvement of systolic and diastolic left ventricular function in non-smokers, while improvement of only systolic function in
smokers. Our study has shown that 12 months of oral estrogen replacement therapy may not have a protective role on the
cardiovascular system of postmenopausal women smokers
Background To determine the acute effects on postprandial lipemia and glycemia by supplementing a high-fat meal with either white button (WB) or shiitake (SH) mushroom powder. Methods Nine healthy participants (4-male, 5-female, 23.3±1.3 years, 17.8±6% body fat, 56.2±11.4kg fat free mass) consumed a control hamburger. At one-week intervals, after consumption of a control meal, participants consumed hamburgers in random order, supplemented with 14g of either WB or SH mushroom powder. Peripheral blood for lipids (triglycerides, high-density lipoprotein HDL, low-density lipoprotein LDL), and glucose was obtained at baseline (t=0 hours) and postprandially every two hours for six hours. Data were analyzed using linear mixed effects models. Results Lower LDL levels were observed for both SH and WB burgers compared to the control burger (p=0.0007) over the six-hour period. Mushroom powder content did not alter triglyceride, HDL, or glucose levels. Gender affected triglyceride and HDL levels over the treatment course. Triglyceride levels were higher in males (p=0.0084), and HDL levels were lower in females (p=0.0005). Triglyceride and glucose levels were higher, (p< 0.001 and p< 0.0001 respectively), during the postprandial time course (t=0, 2, 4, 6 hours). Conclusions Supplementing SH or WB mushrooms during a high-fat meal may lower serum LDL levels.
Atherosclerosis is the leading cause of death in the Western World. In clinical practice, treatment and risk factor modification usually begin only after complications of advanced disease have occurred. Pathology studies, however, have shown that atherogenesis begins much earlier and may be evident in the first decade of life. This thesis describes the development of a non-invasive method to study arterial physiology in children and adults, in order to detect early signs of vascular disease in-vivo, in presymptomatic subjects. Endothelial dysfunction is a key early event in the initiation and progression of atherosclerosis in experimental studies, preceding formation of plaques. We have used high resolution ultrasound to study endothelial and smooth muscle function in systemic arteries in man. Arterial diameter responses to reactive hyperaemia (with increased flow causing endothelium-dependent dilatation) were compared to the responses to sublingual nitroglycerine (which acts independently of endothelial function). Phantom studies have confirmed the precision of diameter measurements (accurate to 0.1-0.2mm), and serial studies have shown reproducible results within patients between visits (coefficient of variation ≅2.0%). Studies on over 200 control subjects without vascular risk factors showed that flow- mediated dilatation (FMD) occurs, and is inversely related to vessel size (r=-0.80, <0.001). The effect of ageing on arterial physiology was also assessed, and FMD was impaired in normal men older than 40 years and women older than 50 years. Twenty adults with established atherosclerosis all had impaired endothelium-dependent dilatation. Over 400 clinically well children and young adults with recognised risk factors were then studied, including children with familial hypercholesterolaemia and young adult smokers. In most, FMD was reduced compared to the relevant controls, whereas nitroglycerine- induced dilatation was preserved. Conclusions. Endothelium-dependent dilatation is impaired in children and adults with risk factors for atherosclerosis, such as smoking and hypercholesterolaemia. The availability of a non-invasive method for studying arterial physiology will facilitate prospective investigation of the progression or reversibility of early vascular disease.
Objective:
To compare the effects of 1) tibolone, 2) continuous combined oestrogen plus progestogen and 3) placebo on plasma lipid and lipoprotein markers of cardiovascular risk in healthy post-menopausal women.
Study design:
randomised, single-centre, placebo-controlled, double-blind study PATIENTS: 101 post-menopausal women were randomised (1:1:1) into one of three groups taking daily 2.5mg tibolone, continuous oral oestradiol-17β 2mg plus norethisterone acetate 1mg daily (E2 /NETA) or placebo.
Main outcome measures:
Fasting serum lipid, lipoprotein and apolipoprotein concentrations measured at baseline and after 6, 12 and 24 months of treatment.
Results:
Both tibolone and E2 /NETA lowered plasma total cholesterol concentrations relative to placebo. With tibolone, high-density lipoprotein cholesterol (HDL-C) was reduced (-27% at 24 months, p<0.001), the greatest effect being in the cholesterol-enriched HDL2 subfraction (-40%, p<0.001). Tibolone's effect on HDL concentrations was also apparent in the principal HDL protein component, apolipoprotein AI (-29% at 24 months, p<0.001). However, there was no significant effect of tibolone on low-density or very-low-density lipoprotein cholesterol (LDL-C and VLDL-C, respectively). By contrast, the greatest reduction in cholesterol with E2 /NETA was in LDL-C (-22% at 24 months, p=0.008). E2 /NETA reduced HDL-C to a lesser extent than tibolone (-12% at 24 months, p<0.001). Effects on HDL apolipoproteins were similarly diminished relative to tibolone. E2 /NETA had no effect on VLDL-C or on the protein component of LDL, apolipoprotein B.
Conclusion:
Tibolone reduces serum HDL. E2 /NETA reduces LDL cholesterol but not apolipoprotein B, suggesting decreased cholesterol loading of LDL. Any impact these changes may have on CVD risk needs further investigation.
The present study of one year duration was intended for assessment of cardiovascular risk factors among 50 women taking low dose combined oral
contraceptive pill as birth control measure and their comparison with equal number of matched women not consuming any form of hormonal
contraceptives. Their BMI, systolic and diastolic BP, Lipid profile, Fasting blood sugar were estimated and ECG was done in the Department of
Physiology and Department of Gynecology and Obstetrics of North Bengal Medical College and Hospital. Results obtained; expressed as Mean +
SD of women, taking OCP, were: BMI (24.98±3.02), SBP (117.76±6.97), DBP (78.04±7.8), FBS(96.66±10.37), total cholesterol (149.08±49.78),
Triglyceride(122.72±67.42), HDL cholesterol (46.81±7.15), LDL cholesterol (77.65±34.68) VLDL cholesterol (38.74 ± 28.03) and those of
women not taking any hormonal contraceptive pills, were BMI (23.74± 1.54), SBP(117.64 ± 7.50), DBP,( 76.88 ± 9.4), FBS(97.36 ± 11.04), total
cholesterol(139.484 ± 26.17), Triglyceride (98.16±22.84), HDL cholesterol (47.79 ± 7.28), LDL cholesterol(62.53±27.49),VLDL
cholesterol(40.9 ± 24.14). 12 Lead ECG was done in both the groups.
On statistical analysis; no significant differences were found in any parameters among the groups , as p-value in every cases were > 0.05;except
serum LDL cholesterol where LDL cholesterol was significantly higher among OCP users group, with p value < 0.05 (p value=0.018). No
significant difference of ECG findings was found between the case and control groups.
From our study, an inference may be drawn that women using hormonal contraceptives pill for long time have a tendency of weight gain, increased
BMI as well mildly deranged lipid profile and in the long run this may increase the risk of both cardiac and cerebro-vascular risks; which demands
regular checkup.
The present study of one year duration was intended for assessment of cardiovascular risk factors among 50 women taking low dose combined oral
contraceptive pill as birth control measure and their comparison with equal number of matched women not consuming any form of hormonal
contraceptives. Their BMI, systolic and diastolic BP, Lipid profile, Fasting blood sugar were estimated and ECG was done in the Department of
Physiology and Department of Gynecology and Obstetrics of North Bengal Medical College and Hospital. Results obtained; expressed as Mean +
SD of women, taking OCP, were: BMI (24.98±3.02), SBP (117.76±6.97), DBP (78.04±7.8), FBS(96.66±10.37), total cholesterol (149.08±49.78),
Triglyceride(122.72±67.42), HDL cholesterol (46.81±7.15), LDL cholesterol (77.65±34.68) VLDL cholesterol (38.74 ± 28.03) and those of
women not taking any hormonal contraceptive pills, were BMI (23.74± 1.54), SBP(117.64 ± 7.50), DBP,( 76.88 ± 9.4), FBS(97.36 ± 11.04), total
cholesterol(139.484 ± 26.17), Triglyceride (98.16±22.84), HDL cholesterol (47.79 ± 7.28), LDL cholesterol(62.53±27.49),VLDL
cholesterol(40.9 ± 24.14). 12 Lead ECG was done in both the groups.
On statistical analysis; no significant differences were found in any parameters among the groups , as p-value in every cases were > 0.05;except
serum LDL cholesterol where LDL cholesterol was significantly higher among OCP users group, with p value < 0.05 (p value=0.018). No
significant difference of ECG findings was found between the case and control groups.
From our study, an inference may be drawn that women using hormonal contraceptives pill for long time have a tendency of weight gain, increased
BMI as well mildly deranged lipid profile and in the long run this may increase the risk of both cardiac and cerebro-vascular risks; which demands
regular checkup.
Background:
Lipid profiles of men and women change differently during the aging process. Guidelines recommend that dyslipidemia patients should consider screening for hypothyroidism without consideration of age or sex.
Methods:
Data from the sixth Korean National Health and Nutrition Examination Survey were used. A total of 4275 participants without thyroid disease and without a past history of dyslipidemia or dyslipidemia medication were evaluated. The association between thyroid dysfunction and lipid profiles (total cholesterol [TC], low-density lipoprotein cholesterol [LDLC], and triglycerides [TG]) was analyzed by age and sex.
Results:
The prevalence of thyroid dysfunction was significantly different according to TC and LDLC levels (p = 0.003 and p = 0.021, respectively). In women, the weighted prevalence of thyroid dysfunction was significantly different according to levels of TC, LDLC, and TG (p = 0.007, p = 0.016, and p = 0.044, respectively). However, in men, no association was found in any of the lipid profiles. Female participants were divided into two groups using a cutoff age of 55 years. In younger women, the weighted prevalence of thyroid dysfunction was different according to the levels of TC, LDLC, and TG (p = 0.013, p = 0.007, and p = 0.007, respectively). However, in older women, no association was found for any of the lipid profiles.
Conclusions:
The prevalence of thyroid dysfunction was significantly different according to lipid profiles, and this association differed by age and sex.
Este trabajo tiene la intención de indicar, los efectos que la testosterona induce en enfermedades cardiovasculares. En este sentido, datos epidemiológicos, indican una influencia de la testosterona en la incidencia de esas patologías. Como ejemplo, se ha propuesto que personas con infarto de miocardio mostraron niveles bajos de testosterona y que esto puede ser un factor de riesgo para enfermedades cardiovasculares en hombres. Otros estudios muestran que la testosterona induce vasoconstricción en arterias coronarias aumentando la densidad de receptores al TxA2. Otra línea de investigación muestra que niveles bajos de testosterona pueden estar asociados con niveles bajos de lipoproteínas de alta densidad. Es claro que el mecanismo de acción de la testosterona y el sitio celular de acción a nivel cardiovascular no es conocido completamente y su caracterización ha sido relativamente muy complicada debido a que este andrógeno induce efectos a largo plazo y efectos a corto plazo.
Este trabajo tiene la intención de indicar, los efectos que la testosterona induce en enfermedades cardiovasculares. En este sentido, datos epidemiológicos, indican una influencia de la testosterona en la incidencia de esas patologías. Como ejemplo, se ha propuesto que personas con infarto de miocardio mostraron niveles bajos de testosterona y que esto puede ser un factor de riesgo para enfermedades cardiovasculares en hombres. Otros estudios muestran que la testosterona induce vasoconstricción en arterias coronarias aumentando la densidad de receptores al TxA2. Otra línea de investigación muestra que niveles bajos de testosterona pueden estar asociados con niveles bajos de lipoproteínas de alta densidad. Es claro que el mecanismo de acción de la testosterona y el sitio celular de acción a nivel cardiovascular no es conocido completamente y su caracterización ha sido relativamente muy complicada debido a que este andrógeno induce efectos a largo plazo y efectos a corto plazo.
The purpose of present study was to investigate the relationships of lipids, lipoprotein and apoprotein parameters to sex hormones, sex hormone-binding globulin (SHBG), insulin resistance, obesity indices, and physical fitness in 34 elderly women aged between 60 and 74 years old. None of the subjects were taking medication known to influence lipid, glucose or hormone levels, and none of them smoked and drank alcohol. Both free testosterone (Free T) and estradiol (E2) were positively correlated to waist to hip ratio (WHR). The SHBG was negatively associated with body mass index (BMI), percentage of body fat (%fat), and WHR, and positively with estimated maximum oxygen uptake (VO2max). Both insulin resistance evaluated by HOMA model (HOMA-R) and fasting insulin concentration (FIRI) were positively related to BMI and %fat. The Free T level was positively correlated to the low density lipoprotein-cholesterol/high density lipoprotein-cholesterol ratio (LDL-c/HDL-c) and the apoprortein B (ApoB) to ApoA1 ratio (ApoB/ApoA1), and negatively correlated with ApoA1 and ApoA2. The SHBG level was positively associated with HDL2-c and HDL2-c/HDL3-c, and negatively with ApoB and ApoB/ApoA1. Both HOMA-R and FIRI were negatively correlated to HDL-c and HDL2-c, and positively with LDL-c/HDL-c, triglyceride, ApoB, and ApoB/ApoA1. The VO2maxwas positively associated with ApoA2, and negatively with ApoB/ApoA1. Multiple regression analysis for lipips, lipoproteins, and apoproteins as the dependent variable was performed. All regression models included the following varibles as the potential independent variable; BMI, %fat, WHR, VO2max, sex hormones, or SHBG. In addition, model A included HOMA-R and model B included FIRI. In model A, both Free T and HOMA-R were independent predictors of LDL-c/HDL-c and ApoB/ApoA1. The HOMA-R was a only independent predictor of HDL-c, HDL2-C, and ApoB. The SHBG and VO2max were independently associated with HDL2-c/HDL3-c and ApoA2, respectively. In addition, E2 level was also one of the independent predictors of ApoB/ApoA1. In model B, both Free T and FIRI were independent predictors of ApoB/ApoA1. The FIRI was a only independent predictor of HDL-c, HDL2-c and ApoB. Both Free T and VO2max were independently and positively correlated to ApoA2. The SHBG was independently and positively associated with HDL2-c/HDL3-c. These results suggest that lipid characteristics in elderly women might be associated with insulin resistance and/or hyperinsulinemia, and the sex hormone profile of so-called “relative hyperandrogenicity” such as levels of increased Free T and decreased SHBG.
During the first decade of the twentieth centry, a series of classic experiments performed by the noted European embryologists Fraenkel, Loeb, Bouin, and Ancel unequivocally demonstrated the essential role of the corpus luteum in the establishment and maintenance of pregnancy (reviewed in 1,2). Subsequent investigations in the 1920s revealed that organic extracts of the corpus luteum were able to elicit the distinctive histological and physiological phenotype of the endometrium (termed “progestational proliferation”), characteristic of early pregnancy in ovariectomized (OVX) rabbits (reviewed in 3). If the animals were mated 1 d prior to ovariectomy, chronic administration of these extracts was sufficient to maintain normal development of the embryo to term. In the early 1930s, the “internal secretion” of the corpus luteum, responsible for these utero-morphic changes was identified and purified by Willard M. Allen at the University of Rochester, NY, which he names “progestrin,” a substance that favors gestation (4). The discovery of progestin, or progesterone, heralded a new era in reproductive medicine, and it was initially envisioned that the hormone would be used to reduce or inhibit such female fertility disorders as spontaneous miscarriages in women at high risk (reviewed in 5). Ironically, during the following decades, the use of progesterone (in derivative form) as a female contraceptive agent (“the pill”) would overshadow its original promise as a fertility drug (6,7).
The incidence of cardiovascular disease in women is negligible before natural or surgically induced menopause [1] and increases after menopause. Epidemiological data suggest that estrogen replacement therapy reduces the occurrence of coronary disease and perhaps cerebrovascular disease by nearly 50% in treated women compared to nonusers. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls [2,3]. Early reports suggested that up to 60% of the protective effect of estrogens on coronary artery disease was attributable to favorable changes in plasma lipids. Reanalysis of the data indicated that the lipid changes probably account for approximately 25% of the cardioprotective effect of estrogens, and that other effects are therefore likely to be important [4]. It is evident that the effect on plasma lipids cannot fully explain the beneficial effects of estrogens upon cardiovascular disease. The influence of estrogens upon carbohydrate metabolism, atheroma formation, and cardiovascular hemodynamics may also play an integral role in the overall beneficial effect of the hormones.
Coronary heart disease (CHD) is the leading cause of death in both pre- and postmenopausal women in Western societies. Both natural and surgical menopause are associated with increased risk of CHD (1), although estrogen replacement therapy (ERT) reduces the risk of CHD by about 50% in postmenopausal women (2–4) and the amount of atherosclerosis by about 50% in animal models (5–8). Even though there is overwhelming evidence that estrogen monotherapy markedly reduces the risk of CHD in postmenopausal women, the effects of estrogen/progestin regimens on CHD risk are less clear. A progestin is added to the ERT regimen to reduce the risk of endometrial cancer, and this may detract from estrogen’s beneficial effects. For example, numerous observational studies as well as meta-analyses (2,4) have concluded that ERT reduces risk of CHD. Reports from the Nurses Health Study (9) found similar reductions in CHD risk with ERT and combined estrogen/progestin treatment (HRT); however, a report of the first randomized, blinded, secondary prevention trial the Heart and Estrogen/progestin Replacement Study (HERS)—found no significant differences between CHD events in the placebo group compared with a group treated with combined, continuous estrogen/progestin (conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) (10).
The purpose of this chapter is to present a perspective on androgenic disorders that emphasizes their broad health implications. Even though their exact incidence is not known, androgenic disorders clearly comprise the most common endocrinopathy of premenopausal women. For this reason the impact of androgenic disorders on the health of women merits serious attention. Most concern has been focused on the associated infertility, and treatment for this aspect has reached a considerable degree of refinement. The androgenic disorders are not always taken seriously as health prob¬lems, perhaps because their most evident effects are on appearance. Although there is treatment for the effects of androgens on appearance, it is complex and not always readily available to women seeking medical help.
Benefits of short term hormone replacement therapy (HRT) include the relief of symptoms of peri-menopausal vasomotor instability and vaginal atrophy. Improvement in cognitive functioning has been reasonably well established (1). Controlled clinical trials have demonstrated that estrogen (E) halts loss of bone mass at menopause and thereafter, yet there is no clinical trial evidence that HRT prevents fractures (2).
Objective
To undertake a comprehensive evaluation of apolipoprotein risk markers for cardiovascular disease (CVD) according to gender, age and menopausal status. DesignCross-sectional analysis of independent associations of gender, age and menopause with serum apolipoproteins. ParticipantsApparently healthy Caucasian premenopausal (n = 109) and postmenopausal (n = 252) women not taking oral contraceptives or hormone replacement, and Caucasian men (n = 307). MeasurementsSerum apolipoprotein (apo) B, A-I and A-II concentrations were measured, plus serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), triglycerides, cholesterol in HDL subfractions and the apoB/apoA-I, LDL-C/apoB, HDL-C/apoA-I and HDL-C/apoA-II ratios. Analyses were undertaken with and without standardization for confounding characteristics and in 5-year age ranges. ResultsOverall, apoB concentrations were highest in men but in women rose with age and menopause to converge, in the age range of 50-55 years, with concentrations in men. The LDL-C/apoB ratio was generally higher in women than in men. ApoA-I concentrations were highest in postmenopausal women and lowest in men (standardized median (IQR) 144 (130, 158) vs 119 (108, 132) g/l, respectively, P < 0001). ApoA-II concentrations were also highest in postmenopausal women but were lowest in premenopausal women (403 (375, 445) vs 329 (305, 357) g/l, respectively, P < 0001). Nevertheless, postmenopausal women had HDL-C/apoA-I and HDL-C/apoA-II ratios approaching the lowest ratios, which were seen in men. Conclusions
Consistent with adverse effects on CVD risk, male gender, ageing in women and menopause were associated with increased apoB concentrations, and menopause and male gender were associated with a decreased cholesterol content of HDL particles.
The purpose of this chapter is to review the research literature, examining and analyzing gender differences with respect to the amounts and types of physical activity needed to decrease morbidity and to promote health and independence in older adults. In epidemiological studies, the dose of physical activity required for beneficial effects has been assessed in terms of the total energy expenditure, the duration or energy expenditure of physical activities termed exercise, or the fitness levels achieved. The terms physical activity, exercise, and physical fitness have distinct definitions, and their differences may have distinct effects on outcome measures as well. Physical activity is defined as any bodily movement produced by skeletal muscle that results in energy expenditure. Exercise, a type of physical activity, is planned, structured, and repetitive bodily movement undertaken to improve or maintain one or more components of physical fitness. Physical fitness is a set of attributes that people have or achieve relating to their ability to perform physical activity. The majority of the literature has focused on physical activity measurements (using questionnaires to accommodate large surveys) and the amounts and types of physical activity needed to prevent disease and promote health. Whether the physical activity is classified as exercise is determined by the quantity or intensity of physical activity, or is reflected in the measurement of physical fitness levels.
Cardiovascular disease is more common in men than in menstruating women, and more common in women with elevated serum androgen levels, as in polycystic ovary syndrome (PCOS) (1) or type 2 diabetes (2) than in normal women. Interest in the relationship between androgens and cardiovascular disease has been stimulated further by the emerging use of testosterone replacement for older men because of concern that cardiovascular risk might increase as a side effect of therapy. The relationship between circulating androgens and the cardiovascular syndrome is intimately related to sex hormone-binding globulin (SHBG) and its downregulation in obesity and by insulin. In fact, SHBG is an indicator of the association between sex hormones and plasma lipids, and low levels of SHBG predict the development of type 2 diabetes. Thus, low testosterone and low SHBG are a part of the metabolic cardiovascular syndrome, and, therefore, testosterone replacement has been advocated in these men to reduce their risk for developing coronary vascular disease. In this chapter, the endocrine regulatory mechanisms that provide insight into this controversy, the epidemiological studies that evaluated the relationship between circulating testosterone levels and risk factors for atherosclerotic cardiovascular disease, measures of subclinical atherosclerosis, and cardiovascular disease end-points are reviewed. Also reviewed are recent animal and laboratory experiments that provide insight into how testosterone may influence the atherosclerotic disease process.
In 23 young males Lp(a) levels before and after application of testosterone have been studied. Testosterone (Testoviron Depot 250) was given at a dose of 2 x 250 mg with a 10 day interval (n = 14) or 6 x 250 mg with 7 day intervals. Lp(a) was measured by radioimmunoassay (Pharmacia-LKB, Freiburg). The test was standardized using a commercially available standard (Immuno, Heidelberg). Statistical comparisons were done by the non parametric Wilcoxon test. The testosterone treatment resulted in a slight elevation of LDL-cholesterol (+5%) as well as significant reductions of HDL (-10%, p = 0.013) and Lp(a) (-18%, p = 0.008) levels. Remarkably the change in Lp(a) was larger than changes in HDL or LDL. The mean Lp(a) concentration (n= 19) decreased from 30.2 to 24.7 mg/dl, the median from 13.5 to 11.1 mg/dl. In four subjects no Lp(a) could be detected (LT2 mg/dl). These data confirm that Lp(a) and LDL levels are independently regulated and accordingly have to be modulated pharmacologically by different principles.
The leading causes of death in postmenopausal women in the United States are coronary heart disease (CHD) and stroke, despite a steady decline during the past two decades [1, 2]. Cardiovascular disease (CVD) secondary to atherosclerosis occurs in much lower frequencies in many third world countries, as well as in several oriental populations [3]. The prevalence of CVD in premenopausal women is reflected by between a fifth and half as many deaths in CHD below the age of 50–55 years, as in men of the same age. After menopause, women develop CHD at the same rate as men, although approximately 6–10 years later [4]. The incidence of stroke is increased with age in both sexes, and most types of stroke are slightly more common in men than in women [5]. Despite the impact of CVD on postmenopausal womens’ health, very few population-based studies of CVD have included women, or focused exclusively on women. Furthermore, few clinical trials have involved female populations large enough to allow adequate evaluation of treatments for CVD in women [2].
Many studies have shown that the prevalence and onset of coronary heart disease (CHD) is sex-dependent. CHD prevalence is lower in women than in men at all ages. Furthermore, women's age of CHD onset seems to be 10 yr later. This is widely attributed to the fact that men have less favorable CHD risk factors (eg, plasma lipid profile) compared to women. Mean levels of protective high density lipoprotein cholesterol are lower, while triglyceride levels are higher in men than in women. It is possible that many of the genes involved in lipid metabolism, such as Apolipoprotein (Apo) E, as well as their polymorphisms, may be expressed in a sexually dimorphic manner. The human Apo E gene is polymorphic, encoding one of 3 common epsilon (epsilon) alleles (epsilon 2, epsilon 3, epsilon 4), with the epsilon 3 allele occurring most frequently (78%) in the Caucasian population. Association studies have shown a protective effect on CHD in epsilon 2 carriers and a harmful effect in epsilon 4 carriers. However, there are conflicting results regarding such allelic effects in respect to gender. This review is focused on the gender-related influence of Apo E polymorphism in respect to plasma lipid levels and the risk of CHD. Additionally, an effort is made to determine if this relation exists and if it can be satisfactorily explained. The studies cited here demonstrate a complex, multifactorial association between these factors, in need of further corroboration in greater population samples.
Although cardiovascular disease remains the number one cause of death in the elderly in the United States, many individuals are living to an older age relatively free of this disease. The purpose of this study was to measure serum lipid and lipoprotein levels in a healthy elderly sample population. We quantitated serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and its suhfractions HDL2 and HDL3, triglycerides, and apolipoproteins A-I and B and calculated low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol in 57 healthy elderly subjects (37 women and 20 men). We found that women had significantly higher levels of HDL-C, HDL2, HDL3, and apolipoprotein A-I than men. In addition, TC and LDL-C levels were significantly higher in persons 75 years and older than in those 65 to 74 years old.
We examined age-related changes of serum lipids and their distribution in each lipoprotein fraction in normolipidemic healthy adults (182 males, 191 females) including 59 octogenarians and 23 nonagenarians. Lipid distribution was analyzed using the agarose gel electrophoresis-enzymatic staining method. The relationship between the lipoproteins, postheparin lipolytic activity and sex hormones was examined in 76 randomly chosen subjects.
The total cholesterol (TC) levels peaked in the 7th decade in males (190mg/dl) and in the 6th decade in females (203mg/dl). It then decreased gradually in both groups. The triglyceride (TG) levels in males showed no changes except for a slight decline in the 10th decade. The TG levels in females increased with age and exceeded those of males after age 70.
The TG distribution showed characteristic changes after age 80. In males, VLDL-TG (%) remained at about 60% for ages 20-59, then decreased to 36.8% at the 9th decade and 25.6 at the 10th decade. LDL-TG (%) was nearly 30% for ages 20-59, and then increased to 50.2% at the 9th decade and 63.5% at the 10th decade. In females, the changes of VLDL-TG (%) and LDL-TG (%) were similar to those in males, but the degree of change was smaller.
Lipoprotein lipase activities of postheparin plasma did not change remarkably in either sex. Hepatic triglyceride lipase (H-TGL) activites in males were constant at about 8μmols FFA/ml/hr for ages 20-59. They then decreased remarkably to 3.3μmoles after age 80. In females, the activities also decreased after age 60. H-TGL activities showed a positive correlation to VLDL-TG (%) (male: r=0.679, p<0.001, female: r=0.323, p<0.05) and a negative correlation to LDL-TG (%) (male :r=-0.574, p<0.001, female: r=-0.347, p<0.05).
The levels of DHEA-S decreased steadily with age in both sexes, and were very low after age 80. DHEA-S showed a significant correlation to VLDL-TG (%) (r=0.516, p<0.01), LDL-TG (%) (r=-0.501, p<0.01) and H-TGL activities (r=0.596, p<0.001) in males.
In conclusion, the increase in LDL-TG (%) and the decrease in VLDL-TG (%) detected after age 80 were characteristic age-related changes in the distribution of serum lipids. We suspect that these changes resulted from the stagnation of the remnant derived from TG-rich lipoproteins, and that the stagnation was affected by the decline of H-TGL activities and DHEA-S levels.
We have heard convincing evidence this morning of the alterations in plasma lipids induced by a broad range of oral contraceptive preparations. Because of the epidemiological association between atherosclerotic cardiovascular disease and hyperlipoproteinemia, hypertriglyceridemia as well as hypercholesterolemia (1), and the possibility that progestational agents may therefore limit the relative immunity from atherosclerosis enjoyed by premenopausal women, we have begun to explore the mechanism of the hypertriglyceridemia of oral contraceptive therapy. These studies, then, evaluate the altered balance between triglyceride (TG) input and removal which result in a raised plasma TG concentration in women given oral progestational agents.
As noted in two previous reports from the Coronary Drug Project,1,2 physicians face a difficult dilemma concerning pharmacologic therapy of hyperlipidemia-hyperlipoproteinemia in an attempt to prevent first or recurrent episodes of clinical coronary heart disease. It is known that susceptibility to premature coronary heart disease is directly related to serum levels of cholesterol, and of low-density and very-low-density lipoproteins. It is also known that elevated serum levels of lipids-lipoproteins frequently can be influenced over long periods of time by available drugs. However, answers to key questions about these pharmaceutical agents are lacking. Do they prevent coronary heart disease and prolong life? Are they reasonably safe in long-term usage?
The Coronary Drug Project—a nationwide collaborative study sponsored by the National Heart and Lung Institute—is the most extensive effort ever undertaken to answer these questions with regard to men who have already experienced one or more episodes of myocardial infarction.¹⁻⁵
A concept that the low density (LDL) and high density (HDL) lipoproteins of the blood plasma are products of triglyceride transport in chylomicrons and very low density lipoproteins (VLDL) and not primary secretory products of cells has been recently developed by us (Eisenberg et al. 1978a, 1978b; Eisenberg 1979a). The concept assumes that chylomicrons and VLDL are the primary lipoproteins synthesized and secreted by cells in normolipidemie states. It is further assumed that both LDL and HDL are by-products of the process of fat transport, the former being a final “core remnant”, and the latter a final “surface remnant” of the triglyceride-rich lipoproteins. This concept is presented schematically in Figure 1 and is described and discussed here.
Weiss, N. S. (National Center for Health Statistics, Rockville, Md. 20852). Relationship of menopause to serum cholesterol and arterial blood pressure: The United States' Health Examination Survey of adults. Am J Epidemiol 96: 237-241, 1972.-The records of 897 40-51-year-old women were selected from the United States' Health Examination Survey, 1960-1962. Women whose menstrual periods had stopped had higher levels of serum cholesterol and diastolic blood pressure, but not systolic blood pressure, than premenopausal women. Among the postmenopausal women, serum cholesterol and blood pressure levels were not related to type of menopause (spontaneous vs. operative) or time interval since menopause. Taken together with other evidence, the results suggest that the menopause precedes the rises in serum cholesterol and diastolic blood pressure. However, because of the cross-sectional nature of this study, it is not yet possible to be certain of the temporal sequence of these events.
The relation of menopause to cardiovascular disease incidence was examined in women less than 55 years old from the cohort of 2873 women in the initial Framingham examination. Although the number of person-years of experience during the 20 years of observation was nearly the same for premenopausal and postmenopausal status, there were only 20 cardiovascular events among the premenopausal women in this age group whereas 70 events occurred among the postmenopausal women of the same age. In each specific age group studied incidence rates were lower in premenopausal than postmenopausal women. This was also true for coronary heart disease. Contrast for "hard" diagnoses of cardiovascular disease (excluding diagnoses of angina pectoris and intermittent claudication) was in the same direction. Although cholesterol and hemoglobin did rise somewhat more steeply in women undergoing the menopause, this greater incidence of cardiovascular disease in postmenopausal women could not be explained by the influence of the menopause on the usual cardiovascular risk factors.
• An alteration in sex hormones has been considered a risk factor for myocardial infarction. In this study, estradiol (E2) and testosterone (T) levels were evaluated in healthy firefighters, patients with myocardial infarction acutely and during their convalescence, patients with no evidence of occlusive coronary artery disease on arteriography, and patients with chronic angina pectoris in whom there was at least one vessel that indicated 50% occlusive coronary artery disease. Although T levels were similar in all groups, E2 levels were substantially higher in patients with myocardial infarction and in patients with chronic angina pectoris. These results support the hypothesis that elevated estrogen levels may be a risk factor for myocardial infarction and coronary artery disease, possibly by promoting clotting or coronary spasm.
(Arch Intern Med 1982;142:42-44)
In this lecture a partial and tentative examination has been made of chemical factors possibly important in the pathogenesis of atherosclerosis. The discussion has centered about four observations concerning the incidence and extent of the disease. The first is that man appears to be unique among mammals in his predisposition; the second, that the condition is seldom if ever seen in the human infant at birth; the third, that healthy women are not likely to develop its complications before the time of the menopause; the fourth, that in man certain maladies and particularly diabetes, familial xanthomatosis, and nephrosis favor early and extensive atheromatous deposits.
An attempt has been made to relate present knowledge of lipid composition of the blood to known variations in the degree of predisposition to the disease. This has included scrutiny of observations on concentration of cholesterol and the Sf 10-20 bodies of Gofman, on cholesterol-phospholipid ratios and on the distribution of cholesterol between the lipoproteins of plasma.
It has been shown that in mammals which never develop spontaneous atherosclerosis the values of all the criteria of concentration and distribution of lipids differ from those of man. Among human beings only the infant at birth has plasma which in its lipid composition closely resembles that of immune mammals. In young women the deviation is less than in other human adults. In groups of patients that display the greatest tendency to the development of atherosclerosis, the plasma lipid patterns differ most widely from those of other mammals.
Among survivors of myocardial infarction many but not all display striking abnormalities in every one of the criteria of lipid concentration and distribution. Comparison of the different methods indicates that in survivors of infarction the distribution of cholesterol between the lipoproteins is more constantly disturbed than the other chemical factors. No test however deviates with sufficient constancy to permit its use in the clinical diagnosis either of the presence of atherosclerosis or of a tendency to its development.
It has been shown that the lipid patterns in man are not immutable but can be manipulated to a considerable degree. Specifically, it has been demonstrated that the administration of estrogen can convert the highly pathologic patterns of survivors of myocardial infarction to normal adult human values, and that the use of methyl testosterone exaggerates the chemical pathology of myocardial infarction and may even produce deviant patterns in those who have been previously normal.
Although the observations which have been reviewed offer strong evidence that predisposition to atherosclerosis is related to deviations in the lipid composition of the blood, they do not establish the chemical hypothesis of pathogenesis. Although at present they lead to no practical applications in therapy, they are regarded as worthy of further investigation with a justifiable hope that greater knowledge may offer new clues to prevention and control.
The effect of noncontraceptive estrogens on the risk of myocardial infarction (MI) in women aged 30 to 49 years was investigated in 477 women with first infarctions and in 1,832 hospital control subjects. There was little evidence of an effect: overall, the estimated relative risk of acute MI for women who had used noncontraceptive estrogens in the preceding month, after allowance for potential confounding factors, was 1.0 (95% confidence interval, 0.6 to 1.7); the corresponding estimate for women who had discontinued use more than one month previously was 1.2 (0.8 to 1.8). There was also no apparent association in various subgroups, including women who smoked heavily and those who had no identified predisposition.
(JAMA 244:339-342, 1980)
We obtained information on 107 women younger than 46 years discharged from a hospital with a diagnosis of acute myocardial infarction. In the series there were 17 women aged 39 to 45 years who were otherwise apparently healthy and had had a natural menopause, hysterectomy, or tubal ligation or whose spouse had had a vasectomy. Among them, nine (53%) were taking noncontraceptive estrogens just prior to admission. Among 34 control women, four (12%) were taking estrogens. The relative risk estimate, comparing estrogen users with nonusers, is 7.5, with 90% confidence limits of 2.4 and 24. All but one of the 17 MI subjects were cigarette smokers. While this illness is rare in most healthy young women, the risk in women older than about 38 years who both smoke and take estrogens appears to be substantial.
(JAMA 239:1407-1408, 1978)
A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I,57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate (100, 200, and 200 mg/mo, respectively, for three months). Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels ( —12.0 mg/dL [ — 0.30 mmol/L]) during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant (not necessarily directly causal) of plasma HDL-C levels during pubertal development.
(JAMA 1987;257:502-507)
There is increasing evidence to suggest that multiple factors, including heredity, occupation, diet, stress, and preexisting hypertension, diabetes mellitus, hypercholesterolemia, and obesity, are involved in the pathogenesis of coronary heart disease. It has also been observed for many years that women have less coronary disease than men. As long ago as 1803, William Heberden recorded that there were only 3 women in nearly 100 patients with pectoris dolor (angina pectoris).1 In a series of 30,000 autopsies, Clawson found a malefemale ratio of 8:1 among patients with coronary sclerosis without hypertension.2 Clinical studies of coronary heart disease have also shown a sex difference, Levy and Boas3 reporting a male-female ratio of 4.9:1, and Master, Dack, and Jaffe4 reporting 3.4:1. These studies have confirmed the observation that women have a decreased incidence of coronary atherosclerosis as compared with men.
Even more striking is the rarity of this disease in women under 40
Thirty-eight post-menopausal women were randomly allocated to substitution treatment with either oestradiol-17β orally (2–4 mg) or cutaneously (3 mg). The concentrations of cholesterol (C), triglycerides (TG) and phospholipids were determined in the high density lipoprotein (HDL)-, the low density lipoprotein (LDL)- and the very low density lipoprotein (VLDL)- fractions twice before medication and after 2, 4 and 6 months of treatment.
Both treatments gave satisfactory clinical results. Oral doses increased the HDL and decreased the LDL thus raising the HDL-C/LDL-C ratio. The higher oral dose also increased the TG concentration. Cutaneous oestradiol gave only minimal changes of the lipoproteins.
The lipoprotein changes observed during treatment with oral oestradiol might reduce the risk for atherosclerotic disease. Therefore, from a lipoprotein point of view, oral oestradiol treatment probably could be considered beneficial. The cutaneous oestradiol treatment had comparable clinical effects without any influence on the lipoprotein pattern.
Replacement therapy with estradiol valerate in 29 post-menopausal women reduced low-density lipoprotein (LDL) cholesterol concentrations by 22% and increased high-density lipoprotein (HDL) cholesterol by 21% after 12 months. Apart from a 67% increase of HDL-triglyceride estradiol had only a slight effect on the levels of lipoprotein triglycerides. Post-heparin plasma lipoprotein lipase (LPL) activity was significantly decreased in subjects with normal pre-treatment very-low-density lipoprotein (VLDL) triglyceride levels, and hepatic lipase (HL) activity was significantly decreased in the group as a whole. It is suggested that estradiol replacement therapy should be considered in climacteric women with high LDL-cholesterol or low HDL-cholesterol levels, or both.
In order to evaluate the relationship between triglyceride-rich lipoproteins (chylomicrons and VLDL) and HDL during alimentary lipaemia, 12 healthy volunteers, 6 male and 6 female (aged 20–40 yrs), were studied. Cholesterol, phospholipid, triglyceride and protein were evaluated in whole serum, VLDL, LDL and HDL (successively subfractionated in HDL2 and HDL3). Blood samples were collected in a fasting state, 4.5 and 9 h after a 1500 calorie meal (20% protein, 40% carbohydrate, 40% fat). A striking increase in triglyceriderich lipoproteins after 4.5 h was observed in both sexes, but was more pronounced in males. An increase in phospholipid and triglyceride as well as a slight reduction in cholesterol was evident in HDL after 4.5 h. At the same time both lipids and proteins were decreased in HDL3 and increased in HDL2. This phenomenon is more evident in females, who showed a significantly higher basal HDL2 level. These results suggest a possible metabolic relationship in the post-prandial phase between triglyceride-rich lipoproteins and HDL, and an inverse correlation between HDL2 and HDL3.
Seventeen postmenopausal women with raised serum total and low-density-lipoprotein (L.D.L.) cholesterol concentrations were treated with œstradiol valerianate for 6 months. Serum-L.D.L.- cholesterol decreased in sixteen patients—the average change at 6 months was -18%. Serum-high-density-lipoprotein (H.D.L.) cholesterol increased by 30% during treatment and the mean H.D.L./L.D.L. cholesterol molar ratio rose significantly from 0·21 to 0·34. There was a significant positive correlation between the size of the decrease in L.D.L. cholesterol and initial L.D.L.-cholesterol concentration. Serum triglyceride and very-low-density-lipoprotein (V.L.D.L.) concentrations were not significantly changed by the treatment. The results suggest that type II hypercholesterolæmia may be taken as another indication for oestrogen therapy in postmenopausal women.
Fifteen men who had had a myocardial infarction between the ages of 32 and 42 years were compared with fifteen age-matched healthy men. Seven of the patients had a strikingly slow rate of beard growth, three had evidence of gynæcomastia, and three had a loss of libido. The slow beard growth and decreased libido, and possibly the gynæcomastia, preceded the myocardial infarction. Mean serum œstradiol and œstrone concentrations were significantly increased in the patients, 43.5±8.8 (standard deviation) and 50.7±9.5, respectively, compared with 33.5±5.5 and 37.5±5.8 pg/ml in the controls (P<0.001). Mean serum testosterone and dihydrotestosterone concentrations were not significantly different in the two groups. Serum œstradiol and œstrone concentrations were directly proportional to each other as were those of testosterone and dihydrotestosterone. These results suggest that the hyperœstrogenæmia preceded the myocardial infarction and that hyperœstrogenæmia may be an important risk factor for myocardial infarction in men.
Between 1910 and 1940, 146 young females, aged 15–30 years, underwent bilateral salpingo-oophorectomy as part of a radical operation for salpingo-oophoritis. These women or their records were reviewed in 1971. 42 women had died in the meantime. More than half (22) of them had died from cardiovascular diseases, 5 from carcinoma of the uterus and 4 had committed suicide. None had died from carcinoma of the breast. Of 68 who were still alive, information by questionnaire was obtained and 32 were admitted to hospital for extensive examination. 32 age-matched women to be operated on for prolapse but with no other known disease of the reproductive tract served as controls. A further control group was added as 11 of the 68 were found to have menstruated again after the operation which had evidently not completely removed the gonads. Complete oophorectomy was found to have been followed by: (a) an increased incidence of cardiac symptoms and nervous diseases as well as an increased use of drugs; (b) a significant increase in the frequency of coronary vascular diseases in ages up to 70 years; (c) an increase in the serum cholesterol and triglycerides, most significantly in the ages below 60-65 years. Women with symptomatic coronary disease had a higher serum cholesterol level than women without and women with signs of peripheral vascular diseases had a significantly higher concentration of serum triglycerides: (d) an increased frequency of fractures (radius and femoral neck), increased osteoporosis and thinner cortical bone. The brittleness of the skeleton was correlated with low excretion of oestrogens in the urine. No vertebral compression or abnormal decrease in height was observed, (e) an increased adrenocortical activity with significantly increased excretion of 17-ketosteroids, 17-OH-ketosteroids and low polar total oestrogens. This activity abated in women above 65 years. (f) a traumatic psychological experience of the accompanying sterility while sexuality seemed to be largely unaffected in many of them. Almost half of the women examined by the psychiatrist were unusually mentally active and agile and they had a lower excretion of estriol than the rest.
Fasting serum lipoprotein lipid concentrations were measured in 64 subjects aged 11-18 and 72 aged 33-54 years, who comprised 86% of long-term residents of these ages in a rural community in Trinidad. Total HDL, HDL2 and HDL3 cholesterol concentrations were similar in males and females after allowance for alcohol consumption. The results differ from other societies in which HDL2 concentration is lower in men than women, and are thought to provide further evidence for interaction between hormonal status and factors such as adiposity and triglyceride concentration with respect to HDL concentration.
Experiments were performed to investigate the lower plasma low-density lipoprotein concentrations seen in premenopausal female populations compared with men or older women. Turnover studies were performed on normal subjects, using their own low-density lipoprotein radioiodinated in the peptide component.Most studies could not be prolonged past 17 days, but it appeared that equilibration of plasma and extravascular compartments was generally incomplete at this stage. In two studies maintained for 6 weeks, equilibration appeared to require more than 3 weeks; turnover rates were slower than has previously been suspected, and the extravascular pool contained about half the total body radioactivity.The 17-day studies appeared to provide quantitatively accurate parameters of lipoprotein fractional catabolic rates (obtained from urinary measurements) but not of plasma half-lives. Ten young women as a group showed significantly faster fractional turnover rates than did 10 men or 3 older women.In men and young women, serum low-density lipoprotein levels had no correlation with fractional catabolic rates, but did correlate with absolute catabolic rates, suggesting that a fixed proportion of the plasma pool may be catabolised daily (although at different rates between the sexes). Results from the 3 older women suggested that a simple relationship between serum low-density lipoprotein levels and absolute catabolic rate may not apply to all age groups. Possible mechanisms of lipoprotein metabolism are discussed in the light of these results.
Plasma lipids, lipoproteins, and anthropometric measurements were assesed in 996 Venezuelan school children (ages 13–18 years) (441 in private, 555 in public schools, Merida, Venezuela) with cross-cultural comparisons to 419 13–18-year-old. American school children from suburban Cincinnati, Ohio. Although there were no systematic differences in plasma cholesterol and triglyceride between public and private Venezuelan school children, low density lipoprotein cholesterol (LDL-C) levels were higher and high density lipoprotein cholesterol (HDL-C) levels lower in public than private school children. Within Venezuelan schools, and between sex, female children had consistently higher total plasma cholesterol, marginally higher HDL-C, and appreciably higher LDL-C than males. There were no consistent cross-sectional changes in lipids and lipoproteins in Venezuelan school children with age.
The V.A. Cooperative Urological Research Group has been engaged in clinical trials of treatment for prostatic cancer for the past 10 years. The first V.A. study showed a much higher risk of cardiovascular disease in patients receiving 5.0 mg of diethylstilbestrol daily than in those receiving placebo. A second V.A. study was begun to compare these treatments with intermediate (0.2 and 1.0 mg/day) doses of diethylstilbestrol. Analyses of survival and cause of death in the second study are presented for 294 Stage III and 214 Stage IV patients randomly assigned to placebo or one of the 3 doses of diethylstilbestrol. Thus far, the 1.0-mg dose has been as effective as the 5.0-mg dose in controlling the prostate cancer, but it does not seem to be associated with the excess risk of cardiovascular death.
Rate zonal ultracentrifugation of plasma samples from ten healthy age-matched volunteers (five males, five females) indicated that the high density lipoprotein subfraction ratio (HDL2:HDL3) in females was significantly higher than in males. The cause of this phenomenon was investigated by simultaneous examination of the metabolism of the major HDL apoproteins (apoA-I and apoA-II) in both groups. The results show that there is no significant sex-related difference in the plasma pool size, fractional catabolic rate, or synthetic rate of either apoprotein. We conclude that the increased HDL2:HDL3 ratio in females versus males does not derive from measurable differences in the metabolic handling of either apoprotein.
To investigate the effects of estrogens and androgens on the metabolism of high density lipoproteins (HDL) and low density lipoproteins (LDL), a normolipidemic postmenopausal woman was studied under the following conditions: (1) during supplementation with ethinyl estradiol (0.06 mg/d); (2) without sex steroid therapy; and (3) during treatment with stanozolol, an androgenic, anabolic steroid (6 mg/d). During these manipulations HDL and LDL cholesterol levels fluctuated widely but reciprocally: during estrogen supplementation HDL increased while LDL decreased; during stanozolol HDL-C decreased while LDL-C increased. Simultaneous changes in post-heparin plasma hepatic triglyceride lipase activity paralleled those of LDL (and opposed those of HDL), decreasing with estrogen and increasing with stanozolol. During all three phases, autologous 125I-HDL turnover studies disclosed similarities between HDL2 and apolipoprotein A-I metabolism and between HDL3 and apolipoprotein A-II metabolism. In the untreated state the residence times of HDL2 and apo A-I were only half those of HDL3 and apo A-II. During estrogen treatment HDL2 and apo A-I, residence times were selectively prolonged, coming to resemble those of HDL3 and apo A-II, which remained unchanged. By contrast, during stanozolol treatment HDL3 and apo A-II residence times were selectively reduced, coming to resemble those of HDL2 and apo A-I, which remained unchanged. Apo A-I levels increased on estrogen and decreased on stanozolol, while apo A-II remained stable. Hence, estrogen increased HDL primarily by retarding the catabolism of the HDL2 subfraction rich in apo A-I, whereas stanozolol decreased HDL by accelerating the catabolism of HDL3, relatively rich in apo A-II. These effects may have been mediated via the concomitant sex steroid-induced changes in the activity of hepatic triglyceride lipase, hypothesized to be a central enzyme in the regulation of HDL catabolism.
Fasting plasma lipid and lipoprotein concentrations were determined in 25 men and 25 women (mean ages 42 and 39 yr respectively) whose exclusive mode of regular exercise was tennis play. When compared to a sedentary group matched for age, sex, and education, the tennis players exhibited similar plasma total cholesterol and LDL-cholesterol concentrations and significantly lower triglyceride and VLDL-cholesterol concentrations. Plasma HDL-cholesterol was significantly higher in the tennis players( in the men and in the women). When we simultaneously controlled for age, relative weight, cigarette smoking, alcohol intake, and oral contraceptive use (in females), the significance of the difference in plasma HDL-cholesterol as well as triglyceride and VLDL-cholesterol concentrations was unaffected in the males but substantially reduced in the females. It is concluded that frequent tennis playing is associated with increased plasma HDL-cholesterol concentrations and that this relationship is independent of other factors known to alter plasma HDL-cholesterol concentration.
Sex differences in cardiovascular disease death rates, as revealed in vital statistics, were reviewed. Analysis was performed by relating male: female ratios to age and by plotting the logarithm of age-specific death rates against age. Although the male: female ratios reach a peak in midlife in most sets of data, the correspondence of this peak with menopause is rather crude. In various nations of the world, the peak sex ratio in deaths from “Arteriosclerotic and degenerative heart disease” was found to range from age 30–35 (Netherlands) to age 55–60 (Japan). The semi-logarithmic plots were very nearly rectilinear under most circumstances, and revealed an absence of an effect by menopause in all cases.
Very low density lipoprotein triglyceride turnover rate, fractional turnover rate, and half-life were studied using Glycerol −3H to label VLD-TG in 16 patients with familial Type IV hyperlipoproteinemia. The patients were maintained on an isocaloric diet with determination of triglyceride turnover after 2 wk of placebo, and a second determination after 2 wk of Oxandrolone (an anabolic-androgenic synthetic steroid). On placebo, mean very low density lipoprotein triglyceride (VLD-TG) was 539, falling on Oxandrolone to (p < 0.05). Mean half-life () was 10.3 hr on placebo and was shortened to 5.2 hr on drug (p < 0.05). The fractional turnover rate (FTR) on placebo was 0.104 ± 0.016 hour−1, and rose to 0.166 ± 0.016 on drug (p < 0.05). Mean turnover rate (TR) rose slightly from 17.6 mg/kg/hr on placebo to 19.04 mg/kg/hr on Oxandrolone. Both postheparin lipolytic activity (PHLA) and postheparin triglyceride lipase (TGL) were appreciably increased on drug, rising respectively from 0.297 μeq FFA/ml/min and 11.7 mμeq FFA/ml/hr (on placebo) to 0.396 and 23.7 (on drug). The changes (Δ) in VLD-TG on Oxandrolone correlated with (R = 0.761) and with Δ FTR (R = −0.532). Oxandrolone may lower very low density lipoprotein triglyc eride by substantially increasing fractional turnover rate and shortening half-life while slightly augmenting turnover rate and improving efficiency of VLD-TG removal.
The effects of stanozolol, 17-methyl-2H-5α-androst-2-eno[3,2-c]pyrazol-17β-ol, on lipoprotein levels were assessed in a short-term (6 wk) prospective study of 10 normolipidemic, postmenopausal, osteoporotic women. While total cholesterol and triglyceride levels remained constant, equal and offsetting responses were seen in low density lipoprotein (LDL) cholesterol (+30.9 ± 28.1 mg/dl [mean ± S.D.], p < 0.01, a 21% increase) and high density lipoprotein (HDL) cholesterol (−32.5 ± 11.9 mg/dl [mean ± S.D.], p < 0.001, a 53% decline). Hence the ratio increased dramatically, from 2.5 ± 0.7 to 6.8 ± 2.5. Within HDL, stanozolol was associated with a greater decline in HDL2 (from 26.0 ± 7.4 mg/dl to 3.8 ± 1.9 mg/dl, p < 0.001, an 85% decrease) than HDL2 (which diminished from 35.7 ± 3.2 to 24.1 ± 5.8 mg/dl, p < 0.001, a 35% decrease). The major HDL apolipoproteins also declined (A-I by a mean of 41% and A-II by 24%, both p < 0.001). Postheparin hepatic triglyceride lipase increased (off treatment 74 ± 42 nmole free fatty acid min−1 mole−1, on treatment 242 ± 110, n = 6, p = 0.06). All changes were reversed by 5 wk following termination of the drug. These lipoprotein changes suggest caution in the long term prescription of stanozolol, particularly in those without overriding clinical indications for its use.
This study encompassed a cross-sectional and longitudinal examination of schoolchildren as they entered into and passed through puberty, examining interrelationships between lipids, lipoproteins, and sexual maturation. In the first year of the study (1976), 529 schoolchildren in grades 5–12 participated; 203 were restudied in 1977, and 141 in 1978. At each yearly visit, the children's stage of sexual maturation was assessed using the Tanner scale. Plasma cholesterol and triglyceride were quantitated each year; high, low, and very low density lipoprotein cholesterol (C-HDL, C-LDL, C-VLDL) levels were measured in the second and third years of the study. In males, cross-sectional decrements in plasma cholesterol were observed with increasing sexual maturation (Tanner stages 1–4), with an increment at Tanner 5 (sexual maturity); plasma triglyceride levels rose at all stages save Tanner 4. The mid-Tanner fall in plasma cholesterol appears (longitudinally) to be accounted for by reduction in C-HDL, while the rise in plasma cholesterol at Tanner 5 may be produced by an increase in C-LDL. Changes in age and Quetelet indices did not appear to relate closely to changes in C-VLDL in 12- and 13-yr-old males, but increasing age and Quetelet indices in 14–15-yr old males accompanied increasing C-VLDL. Cross-sectional studies in females revealed that plasma cholesterol fell at Tanner stages 3 and 4 and rose at stage 5; plasma triglyceride rose during all stages except Tanner 4. Longitudinal studies suggested that the decrements in plasma cholesterol in females may be partially accounted for by reductions in C-HDL; the increase in plasma cholesterol in late sexual development may be accounted for by an increase in C-LDL. In male children, we speculate that the fall in C-HDL and late rise in C-LDL as sexual maturation progresses is associated with increased testosterone production.
The Interrelationships of serum lipids and lipoproteins with measures of body habitus and maturation stages were analyzed in a biracial population of 3151 children, ages 5–14 years. In general, triglycerides, pre-β-lipoprotein, and β-lipoprotein were positively correlated with body habitus and maturation while a-lipoprotein was negatively correlated. The relationships in most instances were more apparent in whites than in blacks, with the highest correlations observed in white boys. No significant correlations were observed between serum cholesterol and the anthropometric variables except in white boys. The most obese children tended to have higher levels of triglycerides, pre-β-lipoprotein, and β-lipoprotein, and lower levels of α-lipoprotein than the remaining population. In the total population, the multiple correlation coefficients with the children's age, race, sex, weight-height Index, triceps skinfold and maturation stage as the independent variables and the concentrations of the different serum variables as the dependent variables ranged from 0.04 to 0.11.
The effect of bilateral oophorectomy upon serum lipids was studied in 25 women, whose average age was 48 years. One month after castration the triglyceride level was significantly (p<0.01) higher than before the operation. Six months later the triglyceride level had fallen slightly and the difference from the preoperative level was no longer significant. Castration did not have any significant effect on serum cholesterol and phospholipids during the seven month follow up period. The effect of peroral estradiol valerate was studied in the same way in 25 women, whose average age was 49 years. Estradiol valerate therapy (2 mg per day) was started one month after castration. After 6 months of treatment the serum phospholipids had increased slightly (p<0.05), buth there was no significant effect on the cholesterol and triglyceride levels.