Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study

Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters.     

Long-term estrogen therapy improves vascular function in male to female transsexuals

OBJECTIVES: This study sought to examine the effects of long-term estrogen therapy on vascular function in male to female transsexuals and to compare the findings with those observed in men and premenopausal women. BACKGROUND: Gender differences in coronary artery disease have largely been attributed to the beneficial effects of estrogen on vascular function and plasma lipids in women. However, the effects of estrogen on the male vasculature have not been widely studied. METHODS: We compared the effects of estrogen on vascular function in 14 male to female transsexuals, 14 age-matched men and 15 premenopausal women. Flow-mediated vasodilation and response to nitroglycerin were assessed in the brachial artery using noninvasive ultrasound. RESULTS: Flow-mediated vasodilation was similar in transsexuals and women but greater than that in men ([mean +/- SE] 11.5 +/- 1.3% and 9.4 +/- 1.1% vs. 5.2 +/- 1.0% respectively, p < 0.005). Responses to nitroglycerin were also greater in transsexuals and women than in men (21.6 +/- 1.7% and 21.0 +/- 0.9% vs. 14.5 +/- 1.2%, respectively, p = 0.0005). These differences persisted even after adjusting for vessel size. Despite similar total cholesterol levels, transsexuals had high density lipoprotein cholesterol levels similar to those in women and greater than those observed in men (1.76 +/- 0.12 and 1.82 +/- 0.11 mmol/liter vs. 1.35 +/- 0.07 mmol/liter, respectively, p < 0.005). Moreover, triglyceride levels were greater in transsexuals than in men and women, and low density lipoprotein cholesterol (LDL-C) particle size was smaller (25.7 +/- 0.2 nm vs. 26.2 +/- 0.1 and 26.6 +/- 0.1 nm, respectively, p = 0.0001). Serum testosterone (an index of estrogen therapy in transsexuals) was markedly suppressed in transsexuals and similar to that in women. Univariate analysis revealed that there was a strong inverse correlation between serum testosterone and flow-mediated vasodilation (r(s) = -0.48, p < 0.005). Multivariate analysis revealed that the best combination of predictors of flow-mediated vasodilation was serum testosterone, vessel size and LDL-C (R2 = 0.3, p < 0.005). CONCLUSIONS: Long-term estrogen therapy appears to improve vascular function in male to female transsexuals and occurs despite higher triglyceride levels and the presence of small, dense LDL-C. The beneficial effects of estrogen are not gender specific or solely mediated through endothelium-derived nitric oxide.     

Estradiol concentrations in premenopausal women with coronary heart disease

BACKGROUND: Because of the beneficial effects of estrogen, premenopausal women are normally protected against coronary heart disease (CHD) and are at lower risk for myocardial infarction; consequently, CHD occurs very rarely in menstrually active women. Given this background, the aim of the present study was to test the hypothesis that decreased concentrations of estrogen are associated with CHD in premenopausal women. METHODS: Fourteen premenopausal women with CHD were investigated and compared with a healthy control group comparable for age and cardiovascular risk factors. Relevant characteristics of patients and controls were assessed: age, blood pressure, body mass index, total cholesterol and high-density lipoprotein cholesterol, triglycerides, former pregnancies, ovariectomy and related surgical interventions, smoking history and former use of oral contraceptives. To ensure the premenopausal status of the participants, the regularity of the menstrual cycle and the follicle-stimulating hormone concentrations were also assessed. Plasma estradiol and progesterone and urine estrone concentrations (24 h urine collection) were measured at day 6 after estimated ovulation to assess the relative increase in plasma estradiol and progesterone during the second half of the menstrual cycle. RESULTS: Compared with the control group, premenopausal women with CHD had significantly lower concentrations of plasma estradiol (408.9 +/- 141 pmol/l and 287.8 +/- 109 pmol/l respectively; P = 0.0228) and total estrogen (2061 +/- 693 pg/mumol creatinine and 1607 +/- 448 pg/mumol creatinine respectively; P = 0.025) in the urine. However, the progesterone concentrations were not significantly different between the groups. These findings might be explained by a partial ovarian dysfunction, as the patient group had a significantly higher number of tubal sterilizations (eight compared with one). CONCLUSION: Our data provide support for the hypothesis that decreased concentrations of estradiol might be an additional pathogenetic factor for the development of CHD in menstrually active premenopausal women.     

Factors associated with an atherogenic lipid profile in premenopausal women without clinical cardiovascular disease

BACKGROUND: To investigate different factors associated to a non desirable lipid profile in premenopausal women without cardiovascular disease. To determine the independent factors of lipid profile as a whole of the sample, for planning preventive studies. PATIENTS AND METHODS: We study (March 1994 to June 1996) premenopausal women with alcohol consumption less than 14 g/day and normal serum level of glucose. Group I: women with a non desirable lipid profile (total cholesterol [TCH, mg/dl]/high density lipoprotein cholesterol [HDL-C, mg/dl] > or = 5). Group II: with a desirable lipid profile (TCH/HDL-C < 5). The following factors were analyzed: age, body mass index (BMI), waist/hip ratio (W/H), systolic blood pressure (SBP, mmHg), fasting plasma insulin (fpI, microU/ml), cigarette smoke (CS) and presence of parents with history of non insulin dependent diabetes mellitus (NIDDM) or hypertension. Statistical methods: Mann-Whitney and Student statistics. Contingency-table analysis (chi 2 statistic). Pearson correlation and multiple linear regression. RESULTS: We analyzed 126 women (age = 30 +/- 8.2; 95% CI, 29-32; TCH = 197 +/- 36; 95% CI, 190-203 mg/dl), with 20 women (group I) and 106 (group II). Women from group I had higher values of W/H (0.83 +/- 0.04 vs 0.78 +/- 0.06; p < 0.001), BMI (29.9 +/- 9 vs 24.6 +/- 4.9; p < 0.03), fpI (12.9 +/- 10.4 vs 7.8 +/- 3.5; p < 0.05), SBP (125.9 vs 117; p < 0.02), as well as higher percentage of smokers (75 vs 40%; p < 0.01) and parents with NIDDM (60 vs 26%; p < 0.01) or hypertension (60 vs 49%; NS). No differences of age were detected (32 +/- 7.3 vs 30 +/- 8.3; NS). BMI (0.32; p < 0.01), W/H (0.50; p < 0.01), SBP (0.27; p < 0.01) and fpI (0.33; p < 0.01) were positively correlated with TCH/HDL-C ratio (n = 126). In multiple regression analysis (n = 126), W/H (regression coefficient = 6.1; 95% CI, 3.1-9.1), fpI (regression coefficient = 0.045; 95% CI, 0.018-0.072) and CS (regression coefficient = 0.5; 95% CI, 0.336-0.667) were the only independent predictors (p < 0.01) of the TCH/HDL-C ratio, controlling a 46% of the variance (R2 = 0.46). CONCLUSIONS: Our data indicates that central obesity, hyperinsulinemia and cigarette smoke are independently associated to a high risk cardiovascular lipid profile in premenopausal women without cardiovascular disease. This study suggests the importance of these factors in the management of early lipid control in these women.     

Plasma lipoprotein and apolipoprotein levels in Taipei and Framingham

We compared the plasma lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apoB, and lipoprotein(a) [Lp(a)] concentrations in a low coronary heart disease (CHD) risk population (n = 440) in Taipei with a high CHD risk population (n = 428) in Framingham matched for age, sex, and menopausal status. Taipei men had significantly lower low-density lipoprotein cholesterol (LDL-C) (-20 mg/dL, -14%, P < .01) and apoB (-7 mg/dL, -6%, P < .05) levels and significantly higher high-density lipoprotein cholesterol (HDL-C) levels (6 mg/dL, 13%, P < .01) than Framingham men. Taipei women had significantly lower LDL-C (-18 mg/dL, -15%, P < .01) and higher HDL-C (4 mg/dL, 7%, P < .01) levels than Framingham women. Median concentrations and distributions of Lp(a) by sex were similar in Taipei and Framingham. After adjusting for body mass index and smoking status, only differences in total cholesterol and LDL-C levels remained significantly different for both sexes between the two populations (P < .01). Gender differences for lipids within populations were similar. After adjusting for age, body mass index, and smoking status, women in both Taipei and Framingham had significantly lower mean triglyceride, LDL-C, and apoB levels and significantly higher HDL-C and apoA-I levels than men. Postmenopausal women in Taipei had significantly higher mean total cholesterol, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) levels than premenopausal women (P < .05), whereas in Framingham postmenopausal women had significantly higher total cholesterol, triglyceride, LDL-C, and apoB levels than premenopausal women (P < .05). Our data are consistent with the concept that plasma lipoprotein cholesterol levels (especially LDL-C) but not apolipoprotein values explain some of the twofold difference in age-adjusted CHD mortality between these two populations.     

Altered regulation of cholesterol metabolism in type I diabetic women during the menstrual cycle

This study examines the relationship of cellular cholesterol metabolism to oestrogen and progesterone during the menstrual cycle in diabetic and non-diabetic subjects. Nine premenopausal diabetic women were compared to nine non-diabetic women of the same age. Oestrogen, progesterone, lipoproteins, including lipoprotein (a) (Lp(a)) and cholesteryl ester transfer protein (CETP) were determined in serum. Cellular cholesterol content and cellular cholesterol synthesis were measured in mononuclear leucocytes. There was no significant change in serum lipoproteins including Lp(a) during the cycle in either group. CETP activity was significantly higher over the 4 weeks in the diabetic patients compared with non-diabetic subjects (mean 463 +/- 30 mumol l-1 h-1 vs 405 +/- 28 mumol l-1 h-1, p < 0.01). Serum high density lipoprotein (HDL) cholesterol was significantly lower during the 4 weeks in the diabetic patients (1.7 +/- 0.1 mmol l-1 vs 1.8 +/- 0.1 mmol-1, p < 0.05). Cellular cholesterol synthesis decreased steadily up to the third week in cells from the control subjects whereas there was no significant change in cells from diabetic patients whose cellular cholesterol synthesis was higher at week 3 compared with non-diabetic subjects (663 +/- 54 nmol mg-1 cell protein vs 432 +/- 43 nmol mg-1 cell protein, two-way interaction p < 0.05). There was a significant negative correlation between cellular cholesterol synthesis and serum oestrogen in the non-diabetic subjects (p < 0.05) but not in the diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central markers of body fat distribution are important predictors of plasma lipids in elderly men and women

We determined the contribution of body fat distribution, peak VO2, fat mass, and dietary intake to variation in plasma lipids in elderly individuals. Volunteers were a healthy cohort of older Caucasian women (n = 75, mean age +/- SD, 72 +/- 5 years) and older men (n = 101, 72 +/- 5 years). We determined fat mass from underwater weighing, fat patterning from waist circumference, as well as peripheral and truncal skinfolds, exercise capacity from peak VO2, and dietary intake from three-day food diaries. Plasma lipid levels were measured in the fasting state and included total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and fasting triglycerides. Older women weighted less than older men, but had higher fat mass, truncal, and peripheral skinfolds. Waist circumference and peak VO2 were lower in older women than older men. Older women had higher total cholesterol (217 +/- 31 vs. 197 +/- 30; p < 0.01), HDL-C (54 +/- 12 vs. 49 +/- 14; p < 0.05), and LDL-C (133 +/- 26 vs. 121 +/- 27; p < 0.01) when compared with older men. No gender differences were noted in fasting triglycerides. Truncal skinfolds were the best predictor of plasma lipids in older men, accounting for between 9% and 30% (r2) of the variation in plasma lipids. Similarly, in older women, central markers of fatness (i.e., waist circumference and truncal skinfolds) were the best predictors of plasma lipids (r2 = 3% to 24%). Total fat mass, peak VO2 and dietary intake were not independent predictors of plasma lipids in older men and women. Indices of central body fatness, rather than total fat mass, peak VO2 or dietary intake are stronger predictors of plasma lipids in healthy older men and women.     

Lipoprotein lipase activity and plasma triglyceride clearance are elevated in endurance-trained women

Numerous studies have examined factors regulating high-density lipoprotein cholesterol (HDL-C) levels in male endurance athletes, but few studies have examined HDL-C regulation in female athletes. The present study compared lipid and lipoprotein concentrations, postheparin lipolytic activities, and the clearance rate (K2) of triglycerides following an intravenous fat infusion in 12 female distance runners (aged 33 +/- 9 years, mean +/- SD) and 13 sedentary women (33 +/- 9 years). Runners were leaner and had greater maximum oxygen uptake values than controls. Runners also had nonsignificantly lower triglyceride (53 +/- 15 v 65 +/- 13 mg/dL) and higher HDL-C (62 +/- 14 v 52 +/- 8 mg/dL, P = .06). Lipoprotein lipase activity (LPLA) was 33% greater (P < .05) and fat clearance (K2) was 27% faster (P < .01) in the trained women, and LPLA correlated directly with K2 (r = .61) and HDL-C (r = .62) in this group (P < .05 for both). K2 was directly related to HDL-C in the athletes (r = .57, P = .06), and also when the active and sedentary women were combined (r = .43, P < .05). These results suggest that increased LPLA and enhanced plasma triglyceride clearance may contribute to the HDL-C levels of physically active premenopausal women.     

Effects of aging and gonadal failure on the hypothalamic-pituitary axis in women

OBJECTIVE: Our aim was to determine the effect of aging on the hypothalamic-pituitary-gonadal axis function. STUDY DESIGN: We studied 9 women aged 25 to 40 years with well-defined idiopathic premature ovarian failure and compared them with 8 women aged 51 to 70 years who had age-appropriate menopause. All women underwent 24 hours of frequent blood sampling every 10 minutes before and after replacement with transdermal estradiol targeted to achieve serum concentrations of approximately 100 pg/ml. RESULTS: In the absence of estrogen exposure, women with premature ovarian failure demonstrated a greater 24-hour mean luteinizing hormone concentration compared with that in the older women with age-appropriate menopause (32.3+/-4.3 mlU/ml vs 19.2+/-2.4 mlU/ml, p=0.0001). Despite the lesser luteinizing hormone serum levels in the older group, the luteinizing hormone pulse frequency per 24 hours was similar (22.1+/-3.0 pulses per 24 hours in prematurely menopausal women vs 21.9+/-2.5 pulses per 24 hours in the older postmenopausal women, p=0.94). When exposed to estrogen, mean luteinizing hormone concentrations decreased to 11.6+/-2.7 mlU/ml in prematurely menopausal women versus 4.4+/-1.0 mlU/ml in older postmenopausal women, p=0.017. Both groups had suppressed mean luteinizing hormone secretion compared with their paired, non-estradiol-exposed studies, p=0.0001. Frequency of luteinizing hormone pulsations was reduced to 16.5+/-3.5 pulses per 24 hours in prematurely menopausal women exposed to estradiol (p < 0.0058, compared with non-estradiol-exposed women). Further reduction was observed in older postmenopausal women (11.5+/-1.1 pulses per 24 hours, p=0.0001, compared with nonestradiol exposure, and p=0.0125, vs prematurely menopausal, estradiol-exposed women). Pulse amplitude was suppressed in both prematurely menopausal women (5.6+/-0.5 mlU/ml to 2.3+/-0.5 mlU/ml, p=0.0001) and older postmenopausal women (3.6+/-0.4 mlU/ml to 2.3+/-0.6 mlU/ml p=0.04) in the presence of estradiol. Although luteinizing hormone pulse amplitudes were greater in the women with premature menopause in the absence of estradiol (p=0.0028) compared with those in older postmenopausal women, pulse amplitudes became similar in the presence of estradiol. Parallel changes in mean follicle-stimulating hormone were observed. Women with premature ovarian failure had a mean follicle-stimulating hormone level of 71.1+/-9.4 mlU/ml that was suppressed to 18.0+/-4.1 mlU/ml after estradiol exposure (p=0.0001); values in older postmenopausal women were 45.9+/-6.0 and 10.3+/-2.0, respectively (p=0.0001). Although the women with premature ovarian failure secreted more follicle-stimulating hormone in the absence and presence of estradiol, only the former situation was statistically significant (p=0.0008 and p=0.23, respectively). CONCLUSIONS: These data suggest that there is an age-related decrease in gonadotropin secretion that may be hypothalamic or pituitary in origin. There is less luteinizing hormone secreted in women older than age 50. There is greater suppression of luteinizing hormone and follicle-stimulating hormone secretion by estradiol in aged women. Thus these data indicate that postmenopausal hormone changes involve central hypothalamic-pituitary alterations, as well as ovarian changes.     

Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes

The risk of coronary heart disease (CHD) is lower in women than in men, but increases in women after menopause. Some of the gender, age, and menopausal-related differences in CHD risk may relate to differences in lipoprotein subspecies. We therefore examined these subspecies in three groups of healthy subjects: premenopausal women (W, n = 72, mean age 41.2 +/- 6.5), postmenopausal women (PMW, n = 74, 55.8 +/- 7.4), and men (M, n = 139, 48.8 +/- 10.7). We measured plasma levels of lipids, lipoprotein cholesterol, apolipoproteins A-I, A-IV, B, C-III, and E, and lipoprotein subspecies Lp A-I, Lp A-I:A-II, Lp B, Lp B:C-III, and Lp B:E, as well as LDL and HDL particle sizes. Our data indicate that women have significantly higher values of HDL-C, apoA-I, apoE, and Lp A-I; larger LDL and HDL particle sizes; and lower values of triglyceride, apoB, and Lp B:C-III particles than men, with no difference in Lp A-I:A-II. Postmenopausal status was associated with significantly higher values of total cholesterol, triglyceride, VLDL-C, and LDL-C; increased levels of apoB, C-III, and E; elevated values of Lp B, Lp B:C-III, and Lp B:E; and lower levels of HDL-C along with smaller HDL particle size. Moreover, we noted a strong correlation between LDL and HDL particle size. Our data are consistent with the concepts that male gender confers decreases in HDL subspecies due to lower Lp A-I levels; while postmenopausal status results in higher levels of all apoB-containing lipoproteins (Lp B, Lp B:C-III, and Lp B:E). The lipoprotein alterations associated with male gender and postmenopausal status would be expected to increase CHD risk.     

Intake of trans fatty acids and risk of coronary heart disease among women

Trans isomers of fatty acids, formed by the partial hydrogenation of vegetable oils to produce margarine and vegetable shortening, increase the ratio of plasma low-density-lipoprotein to high-density-lipoprotein cholesterol, so it is possible that they adversely influence risk of coronary heart disease (CHD). To investigate this possibility, we studied dietary data from participants in the Nurses' Health Study. We calculated intake of trans fatty acids from dietary questionnaires completed by 85,095 women without diagnosed CHD, stroke, diabetes, or hypercholesterolaemia in 1980. During 8 years of follow-up, there were 431 cases of new CHD (non-fatal myocardial infarction or death from CHD). After adjustment for age and total energy intake, intake of trans isomers was directly related to risk of CHD (relative risk for highest vs lowest quintile 1.50 [95% Cl 1.12-2.00], p for trend = 0.001). Additional control for established CHD risk factors, multivitamin use, and intakes of saturated fat, monounsaturated fat, and linoleic acid, dietary cholesterol, vitamins E or C, carotene, or fibre did not change the relative risk substantially. The association was stronger for the 69,181 women whose margarine consumption over the previous 10 years had been stable (1.67 [1.05-2.66], p for trend = 0.002). Intakes of foods that are major sources of trans isomers (margarine, cookies [biscuits], cake, and white bread) were each significantly associated with higher risks of CHD. These findings support the hypothesis that consumption of partially hydrogenated vegetable oils may contribute to occurrence of CHD.     

Age-related deterioration in arterial structure and function in postmenopausal women: impact of hormone replacement therapy

Epidemiological evidence suggests that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular diseases in postmenopausal women. In this study, indices of arterial function [total systemic arterial compliance (SAC) and carotid arterial distensibility coefficient (DC)], structure [carotid intima-media thickness (IMT)], and lipid profiles were compared in postmenopausal women on long-term HRT and aged-matched controls. One hundred nine women aged 44 to 77 years taking HRT and an age-matched group of 108 female controls were entered into the study. The two groups were similar for body mass index, smoking status, exercise level, alcohol intake, and blood pressure. Fasting cholesterol, low density lipoprotein, and lipoprotein(a) were reduced and high density lipoprotein increased in the HRT group. IMT increased with age; SAC and DC were reduced with age in both groups. The HRT group had a higher mean SAC (0.42+/-0.02 versus 0.34+/-0.02 U/mm Hg, P=0.0001) and a lower mean IMT (0.67+/-0.01 versus 0.74+/-0.02 mm, P=0.006) than did controls. Subgroup analysis for estrogen versus estrogen plus progestin revealed no differences for SAC and IMT; DC, however, was greater in estrogen-only users. Smokers on HRT had a higher mean SAC (0.41+/-0.02 versus 0.31+/-0.01 U/mm Hg, P=0.008) and a lower IMT (0.65+/-0.02 versus 0.75+/-0.03 mm, P=0.002) than did smokers not taking such therapy. A protective effect of long-term estrogen therapy on age-related changes in arterial structure and function in postmenopausal women was evident in smokers and nonsmokers alike. Progestin appeared to counteract the effects of estrogen on carotid compliance only. Long-term controlled trials are needed to determine the significance of these findings.     

Proton magnetic resonance spectroscopy of linear nevus sebaceus syndrome

OBJECTIVE: The potential effect of ethnicity on the serum lipid profile and lipoprotein(a) [Lp(a)] was studied in a population with chronic spinal cord injury (SCI). STUDY DESIGN: The distribution and correlates of high density lipoprotein (HDL) cholesterol and Lp(a) were studied in a population of 600 subjects with chronic SCI. RESULTS: Mean +/- SEM serum HDL cholesterol was significantly higher in the African American group than in the white and Latino groups (47 +/- 1 vs 40 +/- 1 and 38 +/- 1 mg/dL, p < .0001, respectively). The African American group had a lower serum total to HDL cholesterol ratio than white and Latino groups (4.46 +/- .153 vs 5.18 +/- .168 and 5.40 +/- .140 mg/dL, p < .01, respectively). Mean serum Lp(a) levels were significantly higher in the African American group than in Latino or white groups (29 +/- 2 vs 18 +/- 1 and 15 +/- 1 mg/dL, p < .0001, respectively). Age, duration of SCI, and level and completeness of lesion had no significant effect on serum Lp(a) level. CONCLUSIONS: In a population with chronic SCI, those in the African American group had the highest serum HDL cholesterol concentrations, the lowest serum total to HDL cholesterol ratios, and elevated levels of serum Lp(a) compared with the Latino and white groups. In a population of individuals with chronic SCI, ethnicity was shown to have a major effect on serum lipids and may be used to assist in the determination of cardiovascular risk.     

Seasonal changes in plasma 25-hydroxyvitamin D concentrations of young American black and white women

Seasonal changes in 25-hydroxyvitamin D concentrations were studied in 51 black and 39 white women aged 20-40 y from Boston. Individual measurements were made in February or March (February-March), June or July (June-July), October or November (October-November), and the following February or March (February-March). Samples from the four visits were analyzed in batches at the end of the study. Plasma 25-hydroxyvitamin D was substantially lower in black than in white women at all the time points, including February-March when values were lowest (30.2 +/- 19.7 nmol/L in black and 60.0 +/- 21.4 nmol/L in white women) and June-July when they were highest (41.0 +/- 16.4 nmol/L in black and 85.4 +/- 33.0 nmol/L in white women). Although both groups showed seasonal variation in 25-hydroxyvitamin D concentrations, the mean increase between February-March and June-July was smaller in black women (10.8 +/- 14.0 nmol/L compared with 25.4 +/- 29.8 nmol/L in white women, P = 0.006) and their overall amplitude of seasonal change was lower (P = 0.001). Concentrations of serum parathyroid hormone in February-March were significantly higher (P < 0.005) in black women (5.29 +/- 2.32 pmol/L) than in white women (4.08 +/- 1.41 pmol/L) and were significantly inversely correlated with 25-hydroxyvitamin D in blacks (r = -0.42, P = 0.002) but not in whites (r = -0.19, P = 0.246). Although it is well established that blacks have denser bones and lower fracture rates than whites, elevated parathyroid hormone concentrations resulting from low 25-hydroxyvitamin D concentrations may have negative skeletal consequences within black populations.     

Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease?

The high risk of cardiovascular disease in patients with diabetes mellitus, particularly in those with nephropathy, is not completely explained by classical risk factors. A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease but information on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic patients (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent diabetes [NIDDM]) and 56 non-diabetic control subjects. Other measurements included the prevalence of diabetic complications, glycaemic control, lipid and lipoprotein levels, vitamin status and renal function tests. Patients with NIDDM had higher homocysteine levels than control subjects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 micromol/l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 micromol/l, NS). Univariate correlations and multiple regression analysis showed albumin excretion rate to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropathy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was considered as the mean of the plasma homocysteine for all control subjects (7.5 +/- 2.1 micromol/l) + 2 SD (cut-off = 11.7 micromol/l). Nephropathy was present in 80 % of diabetic patients with fasting hyperhomocysteinaemia. In conclusion, increases in fasting homocysteine in diabetic patients are associated with increased albumin excretion rate, especially in those with NIDDM, thus providing a potential new link between microalbuminuria, diabetic nephropathy and cardiovascular disease.     

alpha-Tocopherol concentrations in plasma but not in lipoproteins fluctuate during the menstrual cycle in healthy premenopausal women

Because premenopausal women experience cyclic fluctuations of plasma carotenoids and their lipoprotein carriers, it was hypothesized that plasma alpha-tocopherol (A-T) fluctuates by phase of the menstrual cycle. Twelve free-living women, with a confirmed ovulatory cycle, were given a controlled diet for two consecutive menstrual cycles. Blood was drawn during the menses, early follicular, late follicular and luteal phases to simultaneously measure serum hormones, plasma lipoproteins and A-T concentrations, and A-T distribution in the lipoprotein fractions. Plasma A-T concentrations were significantly lower during menses than during the luteal phase by approximately 12% in each controlled diet cycle (P < 0.001). Adjustment for serum cholesterol and triglyceride concentrations did not alter these findings. The distributions of A-T in lipoprotein cholesterol fractions were not significantly different by menstrual phase. From 61 to 62% of A-T was concentrated in the LDL fraction, with another 9-14% in HDL2, 17-22% in HDL3 and the remaining 6-8% in VLDL+ IDL. There were no significant differences in lipoprotein cholesterol fractions by menstrual phase, except for a significant increase (P = 0.03) in HDL2 cholesterol from the early follicular to the late follicular phase. Spearman rank correlations from data during the second controlled diet month showed A-T in HDL2 in the late follicular phase was positively correlated with HDL cholesterol in the early follicular (r = 0.88), late follicular (r = 0.86) and luteal phases (r = 0.86) and with luteal apolipoprotein (ApoA-1) level (r = 0.90), and luteal HDL2 cholesterol (r = 0.83). A-T in HDL3 in the early follicular phase was negatively correlated with HDL2 cholesterol (r = -0.96) and ApoA-1 (r = -0.85), whereas luteal A-T in HDL3 was correlated with luteal HDL3 cholesterol (r = -0.79). Late follicular A-T in VLDL was positively correlated with early follicular HDL3 cholesterol and late follicular HDL3 cholesterol (r = 0.83). Fluctuations of A-T concentrations by phase of the menstrual cycle should be taken into consideration in future research concerning premenopausal women and the risk of chronic disease.     

CD40 mediated activation of gingival and periodontal ligament fibroblasts

Lipids and lipoproteins have been associated with breast cancer risk; however, published results have been inconsistent. To clarify these associations, we measured fasting lipids in women undergoing breast biopsies. A case-control study examined the association of fasting levels of lipids with histologically defined breast cancer risk. Four groups of premenopausal women were assembled on the basis of histological appearance of breast tissue: 1) no epithelial proliferation (n = 102), 2) proliferation without atypia (n = 53), 3) atypical hyperplasia or carcinoma in situ (n = 53), and 4) node-negative invasive cancer (n = 102). A postoperative fasting blood specimen was analyzed for cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Demographics, risk factors, diet, physical activity, fasting weight, and skin-fold thickness were measured. Triglyceride levels were significantly higher in women with node-negative invasive cancer (0.94 +/- 1.04 mg/ml) than in those with no epithelial proliferation (0.83 +/- 1.04 mg/ml, p = 0.03). This association persisted after adjustment for age, body size, lipids, reproductive and familial risk factors, and previous benign breast problems (p < 0.01), in keeping with an independent association of elevated triglycerides with breast cancer risk.     

Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Gender differences in myocardial blood flow dynamics: lipid profile and hemodynamic effects

OBJECTIVES: The purpose of the study was to compare myocardial blood flow (MBF) in hyperlipidemic postmenopausal women and age-matched hyperlipidemic men, and to analyze the relationship between cholesterol subfractions and myocardial blood flow in men and women. BACKGROUND: Women are protected from coronary artery disease (CAD) events until well after menopause, in part due to gender-specific differences in lipid profiles. METHODS: To examine the effect of these influences on coronary microcirculation, MBF was quantitated with N-13 ammonia/PET (positron emission tomography) at rest and during adenosine hyperemia in 15 women and 15 men, all nondiabetic, who were matched for age and total cholesterol levels (53+/-4 vs. 50+/-8 years, p = NS, 6.44+/-1.1 vs. 6.31+/-0.85 mmol/liter, or 249+/-41 vs. 244+/-33 mg/dl, p = NS). RESULTS: Women had significantly higher high density lipoprotein (HDL) and lower triglyceride (Tg) levels than did men, and they showed significantly higher resting MBF and stress MBF levels. Significant correlations were found between resting and hyperemic MBF and HDL and Tg levels (r = 0.44, p < 0.02 for stress MBF vs. HDL; r = 0.48, p < 0.007 for stress MBF vs. Tg). Gender was the strongest predictor of hyperemic MBF in multivariate analysis. Women responded to adenosine hyperemia with a significantly higher heart rate than did men, and hemodynamic factors correlated significantly with blood flow both at rest and during stress. CONCLUSIONS: These data suggest that the favorable lipid profile seen in women may be associated with preserved maximal blood flow in the myocardium.     

Effect of pravastatin (10 mg/day) on progression of coronary atherosclerosis in patients with serum total cholesterol levels from 160 to 220 mg/dl and angiographically documented coronary artery disease. Coronary Artery Regression Study (CARS) Group

To evaluate the effect of pravastatin on progression of coronary atherosclerosis in normocholesterolemic patients with coronary artery disease (CAD), 90 patients with CAD and serum cholesterol levels of 160 to 220 mg/dl were randomized into a pravastatin (10 mg/day) group (n = 45) and control group (n = 45) in a 2-year study. The proportions of patients with progression (an increase of > or = 15% in percent stenosis) and regression (a decrease of > or = 15% in percent stenosis) of coronary atherosclerosis were compared between the 2 groups. Of 90 patients, 80 (89%) had a final angiogram: the pravastatin (n = 39) and control group (n = 41). Percent changes in total cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels were significantly greater in the pravastatin group than in the control group (total cholesterol -11 +/- 12% vs 3 +/- 15%, p < 0.01; low-density lipoprotein cholesterol -18 +/- 16% vs 4 +/- 21%, p < 0.01; apoprotein B -5 +/- 20% vs 6 +/- 20%, p < 0.05). The proportion of patients with progression of coronary atherosclerosis was significantly smaller in the pravastatin group than in the control group (21% vs 49%, p < 0.05). The proportion of patients with disease regression did not differ in the 2 groups (3% vs 2%, p = NS). In conclusion, this study indicates that cholesterol-lowering therapy with pravastatin can prevent the progression of coronary atherosclerosis even in normocholesterolemic patients with established CAD.