Age and dynamics of the chief blood lipid indices among the adult population of Leningrad

Variations in the blood levels of total cholesterol (C), triglycerides, low and high density lipoprotein cholesterol ( LDLPC , HDLPC ) and atherogenicity ratio were examined over time in 4841 men and 2323 women living in Leningrad. The mean values of the parameters studied were established for different age groups. Considerable differences were revealed in the blood lipid profile in men versus women. Higher levels of HDLPC and lower concentrations of LDLPC in women under 50 as compared with age-matched men account for a later development and milder course of coronary heart disease in premenopausal women.     

Changes in lipoprotein composition during the menstrual cycle.

Composition of major plasma lipoproteins was studied in 14 normal women during different phases of the menstrual cycle for three consecutive months. The results were compared to measurements in ten normal age-matched men for a comparable period, to delineate possible sex differences in lipoprotein metabolism in young adults. Blood samples were obtained every 3--5 days after a 14-hr overnight fast and processed for determinations of total plasma cholesterol, LDL- and HDL-cholesterol, and apoproteins B and A-1. In premenopausal women, a significant, 10%--25% cyclical suppression of total plasma cholesterol, LDL-Chol, and LDL-apoB occurred during the luteal phase, which was significantly lower than unchanging concentrations found in men at any time interval. HDL-Chol remained in a significantly higher fixed concentration range in the female subjects as compared to the men. These sex differences in lipoprotein metabolism may have relevance to the reduced susceptibility of premenopausal women to atherosclerosis.     

Effects of sex and age on growth hormone response to growth hormone-releasing hormone in healthy individuals

The influence of age and sex on human GH secretion is controversial. In previous studies, serum GH responses to arginine and insulin-induced hypoglycemia were significantly higher in pre- and postovulatory women than in men. In contrast, recent studies suggest that GH responsiveness to GHRH is higher in normal young men than in age-matched women. To clarify the question of sex and age influence on GHRH-(1-44)-stimulated GH secretion, we studied 116 normal women and men (with body mass indexes of 18-25 and 19-26, respectively) between the ages of 18 and 95 yr. The peak serum GH increments after GHRH administration were significantly higher in premenopausal women than in age-matched men (P less than 0.003 for the age group 18-30 yr and P less than 0.03 for the age group 30-50 yr, as assessed by analysis of variance). The responses were not different in postmenopausal women and age-matched men. Multiple regression analysis revealed a significant negative correlation between GHRH-induced GH responses (integrated area under the curve) and age in both women (P less than 0.002) and men (P less than 0.001). In addition, we determined basal serum testosterone, estradiol, cortisol, and PRL levels in all subjects. Multivariate regression analysis of the GH responses to GHRH administration revealed a significant positive correlation (P less than 0.01) between serum estradiol and both GH increase and the area under the GH response curve. No correlation was found between GHRH-stimulated GH secretion and basal serum cortisol, testosterone, or PRL concentrations. Our data clearly demonstrate a marked influence of both sex and age on GHRH-stimulated GH secretion. We found a higher GH increase in premenopausal women compared with age matched-men and an age-dependent decrease in GHRH-stimulated GH secretion in both sexes. Furthermore, in women a significant influence of estradiol on GH secretion after GHRH administration could be demonstrated.     

Usefulness of electron beam tomography to detect progression of coronary and aortic calcium in middle-aged women

Electron beam tomography (EBT) permits the noninvasive quantification of coronary and aortic calcium as a marker of atherosclerosis. Coronary and aortic calcium are strongly related to premenopausal cardiovascular risk factors in middle-aged women. This report evaluates changes in coronary and aortic calcium over an average of 18 months in 80 women. Measurement variation over time and between readings is also evaluated in these women who were followed through the menopausal transition. Eight years after menopause, 80 women (average age 63 years) underwent serial EBT of the coronary arteries and aorta separated by 18 months. Calcium scores were based on the number and density of calcific deposits. Duplicate readings were obtained to evaluate the effect of reading variation on calcium scores. At baseline, the median calcium score was 0 in the coronary arteries and 58 in the aorta. Average change in coronary (+11) and aortic (+112) calcium were significantly different from zero (p < 0.001). Reading variability did not contribute significantly to the variation in calcium scores. Extent of calcium in the coronary arteries was associated with progression of calcium in the aorta (p = 0.013). Both coronary and aortic calcium were significantly associated with premenopausal cardiovascular risk factors. Thus, progression of coronary and aortic calcium using EBT can be observed over a short time in healthy middle- aged women.     

Sex hormones and hypertension

Gender has an important influence on blood pressure, with premenopausal women having a lower arterial blood pressure than age-matched men. Compared with premenopausal women, postmenopausal women have higher blood pressures, suggesting that ovarian hormones may modulate blood pressure. However, whether sex hormones are responsible for the observed gender-associated differences in arterial blood pressure and whether ovarian hormones account for differences in blood pressure in premenopausal versus postmenopausal women remains unclear. In this review, we provide a discussion of the potential blood pressure regulating effects of female and male sex hormones, as well as the cellular, biochemical and molecular mechanisms by which sex hormones may modify the effects of hypertension on the cardiovascular system.     

Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and particle size distribution, CETP activity, and coronary heart disease (CHD) risk were examined in a population-based sample of 1411 men and 1505 women from the Framingham Offspring Study. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (P<0.05) associated with decreased CETP activity. B1B1 men had lower HDL cholesterol (HDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L) men (P<0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (P<0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (P=0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, beta-blocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (P=0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity, and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele.     

Cardiac health and diabetes mellitus in women: problems and prospects

Cardiovascular disease is the leading cause of morbidity and mortality in both genders. Although premenopausal women display a lower prevalence in cardiovascular diseases compared with age-matched men, they lose this 'female advantage' following menopause. There are significant gender differences in a wide spectrum of cardiovascular incidence, ranging from delayed disease onset to higher prevalence of comorbid diseases for females. Several factors have been suggested to contribute to such difference in cardiovascular incidence including sex hormones, gender-specific intrinsic organ function, difference in body size and cardiovascular risk factor profiles (e.g., use of tobacco and alcohol, hypertension, diabetes mellitus, dyslipidemia, obesity, sedentary lifestyle and atherogenic diet). A gender difference also exists for diabetes and diabetic complications. Heart diseases exhibits a 2-fold and a 5-fold increase in men and women with diabetes, respectively. Although female hearts are usually more tolerable to stress insults than their male counterparts, female sex hormone such as estrogen interacts with diabetic risk factors to precipitate cardiomyopathy. This review aims at recaping our knowledge on gender difference in diabetic heart disease with an emphasis on disease pathogenesis. Deficits and obstacles to optimal risk factor management in diabetic women are also discussed in an effort to improve the overall cardiovascular health of diabetic women.     

Acute myocardial infarction in premenopausal women

Prospective, systematic studies of the pathophysiology and prognosis of premenopausal women vs young men who suffer an acute myocardial infarction (MI) and are treated with direct angioplasty are scarce. METHODS AND RESULTS: A total of 782 consecutive and unselected patients who presented with an acute ST-elevation MI within 12 h of symptom onset underwent immediate angiography to guide direct angioplasty. Using this therapeutic approach clinical characteristics, angiographic observations, and short- and long-term prognosis were analyzed in a sub-group of 31 premenopausal women and compared to 192 young men with acute MI. Premenopausal women account for 4% of individuals with acute MI and for 15% (31/205) of all women. Men of the same age range make up 25% (192/782) of all MI patients (p<0.001). Three or more classic risk factors were present in 20/31 women. Young women presented later than men. Angiography demonstrated a coronary occlusion in 27/31 women (88%) but in 98% of young men (p<0.02). Direct PTCA was successful in all premenopausal women and in 179/185 men (97%, p=ns). Predischarge EF was 57% in women and 54% in men (p=ns). After 4 years of follow-up, all women had survived as compared to a 95% survival in young men. Major cardiac events had occurred in 50% of persons of either gender. CONCLUSION: Premenopausal women account for 4% of individuals and for 1/6 of all female patients who presented with acute MI within 12 h of onset. Hospital admittance is delayed in young women. MI was caused by (atherosclerotic) coronary occlusion in most young women and in virtually all young men. Short- and long-term survival of premenopausal women is favorable after direct PTCA for acute MI and not different than men from the same age group.     

Coronary vascular dysfunction in premenopausal women with diabetes mellitus

Background Diabetes mellitus abolishes the sex differential in coronary artery disease morbidity and mortality in premenopausal women. This finding is independent of other diabetes-associated risk factors, suggesting that other mechanisms such as impaired coronary vascular function may contribute to the increased cardiovascular risk in women with diabetes. The objective of this study was to investigate the effect of diabetes on coronary vascular function in premenopausal women. Methods We studied 13 premenopausal women with diabetes (aged 41 ± 10 years) who were free of overt cardiovascular complications, and 21 control women (12 age-matched and 9 postmenopausal [aged 56 ± 8 years]). We used [¹³N]-ammonia as the flow tracer and positron emission testing to measure myocardial blood flow (MBF) at rest, during maximal hyperemia, and in response to cold pressor testing. Results Baseline MBF was lower in the postmenopausal controls, reflecting the differences in cardiac work and oxygen demand as assessed by the rate-pressure product. However, baseline MBFs were similar in the 3 groups after normalization for differences in the rate-pressure product. During hyperemia, MBF increased and coronary vascular resistance decreased significantly in the 3 groups. However, the increase (from baseline) in MBF in the women with diabetes (164% ± 58%) was less than in the premenopausal controls (258% ± 81%, P = .021), but not significantly different from the postmenopausal control women (204% ± 104%, P = .51). Likewise, the increase in MBF in response to cold pressor testing in the women with diabetes (24% ± 19%) was significantly lower than in the premenopausal controls (60% ± 39%, P = .013), but similar to that in postmenopausal control women (27% ± 15%, P = .97). These differences persisted after adjusting for age and diabetes-associated metabolic abnormalities. Conclusions These results demonstrate reduced coronary vasodilator function and impaired response of resistance vessels to increased sympathetic stimulation in premenopausal women with diabetes, similar to those observed in healthy postmenopausal women in whom the sex differential in coronary artery disease morbidity and mortality is no longer present. (Am Heart J 2002;144:711-8.)     

Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women

BACKGROUND: Coronary artery calcium, a radiographic marker for atherosclerosis and a predictor of coronary heart disease (CHD), is less extensive in women than in men of the same age. The role of estrogen in the pathogenesis of coronary artery calcification is unknown. We examined the association of estrogen status with extent of calcification and atherosclerotic plaque in coronary arteries of deceased women. METHODS: Coronary arteries were obtained at autopsy from 56 white women age 18--98 yr, 46 postmenopausal and 10 premenopausal. Exclusion criteria included patients with coronary stents, coronary artery bypass surgery, and medical-legal cases. Medical records were reviewed for demographics, CHD risk factors, menstrual status, and use of estrogen replacement therapy. Contact microradiography of coronary arteries assessed true calcium content and atherosclerotic plaque area was analyzed histologically. RESULTS: The coronary arteries from estrogen-treated postmenopausal women had lower mean coronary calcium content (P = 0.002), mean plaque area (P < 0.0001), and calcium-to-plaque area ratio (P = 0.004) than those from untreated menopausal women. Estrogen status, age, diabetes, and hypertension predicted calcium and plaque area by univariate analysis. After controlling for these CHD risk factors, estrogen status remained an independent predictor of both calcium (P = 0.014) and plaque area (P = 0.001) in all women. Mean calcium area (P < 0.05) but not plaque area (P = 0.44) was significantly greater in women treated with estrogen replacement therapy than in premenopausal women. Coronary calcium (P < 0.007) and plaque area (P < 0.03) varied significantly with age in untreated postmenopausal women, but not in the estrogen-treated or premenopausal women (P = 0.33). CONCLUSIONS: Estrogen status is associated with coronary calcium and plaque area independent of age and CHD risk factors. Estrogen may modulate the calcium content of atherosclerotic plaques, as well as plaque area and may slow the progression of atherosclerosis in women.     

Lipids and Lipoproteins in Women

Atherosclerosis and coronary artery disease (CAD) are the main causes of death in the Western world, for both men and women. However, in premenopausal women CAD is less frequent than in men, but in elderly women (e.g., > 75 years) myocardial infarction (MI) occurs even more often than in men. In summary, women suffer from CAD and MI but at a later age than men. Therefore it is important to observe and compare the cardiovascular risk factors in women and men. The typical CAD risk factors such as hyperlipidemia, smoking, arterial hypertension, diabetes mellitus, obesity, physical inactivity, and unhealthy nutrition are increasingly important for both genders. Many of these factors are comparable between men and women, but due to hormonal influences especially the lipoprotein metabolism shows some striking differences between men and women, but interestingly enough also between pre- and postmenopausal women. Therefore this paper will focus especially on the gender-specific differences in lipid metabolism as a potential target which might explain both the gender-specific and also pre- and postmenopausal differences in the occurrence of CAD.     

Effect of gender on atrial electrophysiologic changes induced by rapid atrial pacing and elevation of atrial pressure

INTRODUCTION: The incidence of atrial fibrillation is greater in men than in women, but the reasons for this gender difference are unclear. The purpose of this study was to evaluate the effects of gender on the atrial electrophysiologic effects of rapid atrial pacing and an increase in atrial pressure. METHODS AND RESULTS: Right atrial pressure and effective refractory period (ERP) were measured during sinus rhythm and during atrial and simultaneous AV pacing at a cycle length of 300 msec in 10 premenopausal women, 11 postmenopausal women, and 24 men. The postmenopausal women were significantly older than the premenopausal women (61 +/- 8 years vs 34 +/- 10 years; P < 0.01). During sinus rhythm, mean atrial ERP in premenopausal women was shorter (211 +/- 19 msec) than in postmenopausal women and age-matched men (242 +/- 18 msec and 246 +/- 34 msec, respectively; P < 0.05). Atrial ERPs in all patients shortened significantly during atrial and simultaneous AV pacing. However, the degree of shortening during atrial pacing (43 +/- 8 msec vs 70 +/- 20 msec and 74 +/- 21 msec; P < 0.05) and during simultaneous AV pacing (48 +/- 16 msec vs 91 +/- 27 msec and 84 +/- 26 msec; P < 0.05) was significantly less in premenopausal women than in postmenopausal women or age-matched men. CONCLUSION: The results of this study demonstrate a significant gender difference in atrial electrophysiologic changes in response to rapid atrial pacing and an increase in atrial pressure. The effect of menopause on the observed changes suggests that the gender differences may be mediated by the effects of estrogen on atrial electrophysiologic properties.     

Mechanisms of Atherothrombosis and Vascular Response to Primary Percutaneous Coronary Intervention in Women Versus Men With Acute Myocardial Infarction: Results of the OCTAVIA Study

ObjectivesThis study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI).BackgroundThere is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age.MethodsIn this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow-up as determined by optical coherence tomography.ResultsMen and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: –0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up.ConclusionsIn patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207)     

Effect of gender differences and estrogen replacement therapy on vascular reactivity

The incidence of cardiovascular disease is lower in premenopausal women compared with men; following menopause, the risk of mortality from cardiovascular disease increases in females. Postischemic dilatation of the brachial artery has been used previously as an index of endothelium-mediated vasodilation. Using this index, we examined a group of premenopausal and postmenopausal women, some of whom were on estrogen replacement therapy (ERT). All subjects were normotensive (blood pressure [BP] <140/90 mm Hg) and normoglycemic (blood glucose, <100 mg/dL). Fourteen healthy women (mean age, 27 +/- 0.8 years; mean total cholesterol, 174 +/- 6.7 mg/dL) and fourteen healthy men (mean age, 26 +/- 1.4 years; mean total cholesterol, 181 +/- 7.2 mg/dL) were investigated. Nineteen postmenopausal women were also examined; 11 were on ERT (mean age, 55 +/- 2.1 years; mean total cholesterol, 213 +/- 6.6 mg/dL) and eight were not on ERT (mean age, 60 +/- 3.6 years; mean total cholesterol, 222 +/- 14.4 mg/dL). Ischemia was induced by inflating a cuff over the forearm to a pressure of 40 mm Hg above systolic for 5 minutes. Doppler ultrasonography (Acuson [Mountain View, CA] 128XP/10c ultrasonograph with a 7.5-MHz linear array transducer) was used to measure the brachial artery diameter before inflation and 15 seconds and 45 to 60 seconds following cuff deflation. Flow-mediated dilatation (FMD%) and hyperemia were defined as the percentage increase over basal diameter and basal flow, respectively. Postischemic median dilatation in men was 4.20% (interquartile range, 2.13% to 5.56%) and 11.48% (interquartile range, 8.70% to 14.29%) in age-matched premenopausal women (P < .01). For women on ERT, the postischemic median dilatation was 8.11% (interquartile range, 6.01% to 11.60%), as compared with 2.82% (interquartile range, 1.32% to 3.28%) for women without ERT (P < .01). Premenopausal women showed significantly greater dilatation after ischemia than postmenopausal women without ERT (P < .0001). Hyperemia was similar in all groups. These findings show that postischemic vasodilation of the brachial artery is greater in premenopausal women versus age-matched men; it is decreased in postmenopausal women, and ERT restores it toward normal. The pathophysiology underlying the diminution in postischemic dilatation may be relevant to atherogenesis and coronary artery disease (CAD).     

Association between postprandial hyperinsulinemia and coronary artery disease among non-diabetic women: a case control study

BACKGROUND: We planned a case-control study to assess the relation of fasting glucose, fasting insulin, postprandial glucose and postprandial insulin levels with coronary artery disease in nondiabetic women. METHODS: Among 968 consecutive nondiabetic women screened, 104 with coronary artery disease (mean age 60, 4+/-9) made up the study cohort (group I). One-hundred and four age-matched, nondiabetic women without coronary artery disease who had a similar lipid and blood pressure profile (group II), and 52 healthy, age-matched women served as controls (group III, real control group). Demographics, waist circumference, lipids, fasting glucose postprandial glucose, fasting and postprandial insulin levels were compared among the groups. A separate subgroup analysis were performed in patients with metabolic syndrome. RESULTS: No differences were identified in terms of prevalences of risk factors between group I and group II. Women with coronary artery disease had higher postprandial insulin level than the women in group II and group III. In reverse stepwise logistic regression analysis postprandial hyperinsulinemia was found to be the single independent determinant for coronary artery disease for the entire study group as well as for women with metabolic syndrome. CONCLUSION: Our data demonstrate that postprandial hyperinsulinemia is independently associated with coronary artery disease, irrespective of fasting glucose, postprandial glucose, and fasting insulin levels in nondiabetic women with clusterings of factors of metabolic syndrome.     

Microvascular effects of CRH in human skin vary in relation to gender.

Males and females have a significantly different life expectancy because of the cardioprotective effects of estrogen. The mechanisms that result in this difference between the sexes are not fully understood. However, stress is a contributing factor to the development of cardiovascular disease, and stress-related factors derived from central or peripheral sources may have differential effects in the modulation of cardiovascular function in males and females. CRH is a central modulator of the stress response and is known to have vasodilator effects in a number of vascular beds. We have examined whether CRH has vasodilator effects in human skin and whether this effect is different between males and females using laser Doppler and iontophoresis. CRH (1 nM) had vasodilatory effects in the skin circulation of both premenopausal females (n = 6) and age-matched males (n = 5), but CRH-induced dilation was significantly more potent in females than males. Acetylcholine (1 nM) and sodium nitroprusside (0.74 nM) induced dilation was not significantly different between males (n = 6) and females (n = 6). This is the first study to demonstrate that CRH acts locally as a vasodilator in human skin circulation and that this response is augmented in premenopausal females. The mechanism by which CRH causes dilation in human skin is presently unknown. However, these data suggest that CRH-induced dilation may be one mechanism by which cardiovascular risk is reduced in premenopausal women.     

Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes

Gender-related differences in the rate of coronary heart disease (CHD) between premenopausal women and men are greatly diminished in women with diabetes mellitus (DM). This may be related, in part, to altered platelet function in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased nitric oxide (NO) destruction, and increased myosin light-chain (MLC) phosphorylation (MLC-P). Accordingly, we investigated functional and biochemical parameters of platelet function in 32 women (14 premenopausal and postmenopausal controls and 18 age-matched patients with DM); platelet MLC-P and cyclic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other parameters including age, body mass index (BMI), waist to hip ratio, total cholesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 +/- 3 fmol/mL in controls v 23.1 +/- 3 fmol/mL in diabetic subjects) and 3 minutes after insulin exposure. The platelet content of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despite similar estradiol (beta,E2) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative stress in this patient population. These observations indicate that an altered redox state and associated MLC-P of platelets does not contribute to enhanced platelet aggregation and CHD in premenopausal women with DM.     

High intake of cholesterol results in less atherogenic low-density lipoprotein particles in men and women independent of response classification

The influence of a high-cholesterol diet on the atherogenicity of the low-density lipoprotein (LDL) particle was examined by measuring LDL peak diameter and composition, LDL susceptibility to oxidation, and the distribution of cholesterol between LDL subclasses. The crossover intervention randomly assigned 27 premenopausal women and 25 men (18 to 50 years) to an egg (640 mg/d additional dietary cholesterol) or placebo (0 mg/d additional dietary cholesterol) diet for 30 days, followed by a 3-week washout period. Subjects were classified as either hyperresponders (>2.5 mg/dL increase in plasma cholesterol for each 100 mg additional dietary cholesterol consumed) or hyporesponders to dietary cholesterol. Sex was found to have a significant effect on 3 of the parameters examined. LDL peak diameter was significantly larger (P <.005) in females (26.78 +/- 0.59 nm, n = 27) as compared with males (26.52 +/- 0.49 nm, n = 25), regardless of response to dietary cholesterol. The LDL particles of the male participants also had a higher number of triglyceride (TG) and cholesteryl ester (CE) molecules (P <.01); however, cholesterol ester transfer protein (CETP) activity was higher in females (P <.05). Response classification also revealed significant differences in the determination of LDL subclasses. Independent of sex, the LDL-1 particle (P <.05), which is considered to be less atherogenic, was predominant in hyperresponders and this finding was associated with increased cholesterol intake (interactive effect, P <.001). In addition, CETP and lecithin: cholesterol acyltransferase (LCAT) activities were higher in hyperresponders during the egg period (interactive effect, P <.05). Sex, response to cholesterol intake, and diet were not found to affect the susceptibility of LDL to oxidation (P > 0.5). Because LDL peak diameter was not decreased and the larger LDL-1 subclass was greater in hyperresponders following egg intake, these data indicate that the consumption of a high-cholesterol diet does not negatively influence the atherogenicity of the LDL particle.     

Mechanisms of Estrogen Effects on the Endothelium: An Overview

In this review, we aim to provide an overview of the recent advances in understanding estrogen effects on the vascular endothelium. Epidemiological studies suggest the female sex hormone estrogen mediates the relative protection of premenopausal women against cardiovascular disease, compared with age-matched men. However, results from clinical trials of exogenous estrogen supplementation in postmenopausal women have been disappointing, generating much controversy about the role of estrogen and demonstrating the need for further research in this field. Here we have discussed the roles of different estrogen receptors (ERs) such as ERα, ERβ, and G-protein coupled receptor 30; the complex genomic and nongenomic signalling pathways downstream to ER activation and the factors such as age, menopause, pregnancy, and diabetes that might alter estrogen responses. The common themes of this discussion are the complexity and diversity of endothelial estrogen responses and their modulation by 1 or more coexisting factors. Finally, we summarize the emerging therapeutic options including improved targeting of individual ERs and signalling pathways that might maximize the therapeutic potential of estrogenic compounds while minimizing their harmful side effects.