Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.     

Premenopausal black women have more risk factors for coronary heart disease than white women

Premenopausal black women have a 2- to 3-fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide greater insight into the reasons for this difference, which are currently unclear. We compared CHD risk factors in 99 black and 100 white, healthy premenopausal women, aged 18 to 45 years, and of relatively advantaged socioeconomic status. Compared with white women, black women had a higher body mass index (32.0 +/- 9.2 vs 29.0 +/- 9.4 kg/m2, p = 0.021), and higher systolic (124 +/- 17 vs 115 +/- 14 mm Hg, p <0.0001) and diastolic (79 +/- 14 vs 75 +/- 11 mm Hg, p = 0.048) blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher in the black women (40.2 +/- 31.3 mg/dl) than in the white women (19.2 +/- 23.7 mg/dl, p <0.0001). The plasma total homocysteine level was also higher in the black women (8.80 +/- 3.38 vs 7.81 +/- 2.58 micromol/L, p = 0.013). The black women, however, had lower plasma triglyceride levels (0.91 +/- 0.46 vs 1.22 +/- 0.60 mmol/L, p <0.0001), and a trend toward higher high-density lipoprotein (HDL) cholesterol levels (1.37 +/- 0.34 vs 1.29 +/- 0.31 mmol/L, p = 0.064) than the white women. Plasma total and low-density lipoprotein (LDL) cholesterol levels were similar, despite a greater consumption of saturated fat and cholesterol by the black women. Rates of cigarette smoking and alcohol intake were low and similar between the races. In summary, premenopausal black women had a higher mean body mass index, blood pressure, lipoprotein(a), and plasma total homocysteine level, and a greater consumption of saturated fat and cholesterol than white women. These differences in coronary risk factors may place the black women in our study at increased risk for CHD compared with the white women.     

Treatment of dyslipoproteinaemia in diabetes mellitus

Coronary heart disease (CHD) is the most common cause of premature death in diabetes. Hypercholesterolaemia occurs in diabetes with about the same frequency as in the general population, but it confers a greater risk of CHD in diabetes. Hypertriglyceridaemia and low serum high density lipoprotein (HDL) cholesterol levels are more common in diabetes, particularly non-insulin-dependent diabetes. Nephropathy increases the severity of dyslipoproteinaemia. There remains a reluctance to apply the results of cholesterol-lowering trials to diabetes. No trial has been specifically in diabetes, but this should not constrain the treatment of diabetic patients at clearly high CHD risk. It is suggested that fasting lipids should be measured in all diabetic patients aged less than 70 years with established CHD or whose non-fasting cholesterol is >6.00 mmol I(-1) or triglycerides >3.00 mmol I(-1). For those with raised lipids glycaemic control should be improved, if possible, and dietary therapy aimed at a decrease in fat intake, particularly saturated fat, and weight reduction in the obese. Lipid-lowering drugs are required in patients with CHD and serum cholesterol >5.5 mmol I(-1) with the aim of decreasing non-HDL to <4.00 mmol I(-1). In patients without CHD lipid-lowering drugs should be considered when serum cholesterol exceeds 6.5 mmol I(-1) and the risk of CHD is greater than 20 % over the next 10 years. There is no evidence that pursuing this policy beyond the age of 70 years is beneficial. Diabetic women with dyslipoproteinaemia should, however, be treated in the same way as men. The knowledge that hypertriglyceridaemia and low serum HDL cholesterol are present helps in the assessment of CHD risk and the choice of medication to decrease non-HDL cholesterol, but there is no evidence that their treatment in the absence of raised cholesterol is of benefit.     

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.     

Poland and United States Collaborative Study on Cardiovascular Epidemiology. A comparison of HDL cholesterol and its subfractions in populations covered by the United States Atherosclerosis Risk in Communities Study and the Pol-MONICA Project

HDL cholesterol (HDL-C) levels are inversely related to coronary heart disease (CHD) risk, and HDL-C distributions vary among countries. Poland is one of the few developed countries in which CHD rates are increasing at the same time that US rates have been falling, but whether these differences are explained by differences in risk factors such as HDL-C has not been determined. To examine this possibility, levels of HDL-C and its subfractions were compared in US and Polish urban and rural men and women aged 45 to 64 years. Age-adjusted HDL-C means were 0.20 mmol/L higher in urban Polish men and 0.37 mmol/L higher in rural Polish men than in their US counterparts (P < .0001); means in urban Polish women were 0.06 mmol/L higher (P < .05) and in rural Polish women 0.09 mmol/L higher (P < .001) than in their US counterparts. Adjustment for age, education, alcohol intake, smoking, BMI, heart rate, and menopause status (in women) had little effect on differences. Means of HDL2 and HDL3 levels showed similar between-country differences, although differences were minimal for HDL2 in urban men and women, and HDL3 means did not differ between rural women. BMI was inversely related to HDL-C and both subfractions in all gender-country-site strata (P < .001), and alcohol was directly related to HDL-C (P < .001) in all strata except Polish women. Cigarette smoking was negatively related to HDL-C and both subfractions in all US samples except HDL2 in urban men, whereas in Polish samples, significant associations were found only in urban women for HDL-C and in rural and urban women for HDL3. Age, heart rate, and education showed inconsistent or no association with HDL-C and its subfractions in either country. This profile of HDL-C and its subfractions in Polish samples contrasts sharply with the opposite trend in CHD mortality rates, which suggests either that other risk factors may account for the trends or that the relationship between HDL-C and CHD may differ between the two countries.     

Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP)

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.     

Italian style brewed coffee: effect on serum cholesterol in young men

BACKGROUND: Increases in blood lipids have been observed in humans when coffee is brewed by the boiling method. The purpose of this study was to evaluate if giving up Italian coffee might reduce blood cholesterol levels. METHODS: Eighty-four normolipidaemic young adult males, after a 3-week baseline (BL), were randomly assigned to three different regimens of coffee consumption: espresso (E), mocha (M), and no coffee, but tea (T). The average coffee consumption during intervention (I) was 3.1 +/- 1.2 and 2.8 +/- 1.1 cups per day for espresso and mocha group respectively (espresso: 25-35 ml/cup; mocha: 40-50 ml/cup). Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were measured eight times during the study. Dietary pattern, alcohol consumption, smoking habits, drug use, and anthropometric data were also recorded. RESULTS: The changes observed in serum cholesterol concentration between baseline and intervention were not statistically different in all groups. The changes were 0.0 mmol/l (T), +0.01 mmol/l (E) and +0.05 mmol/l (M) for total serum cholesterol; 0 mmol/l (T), -0.02 mmol/l (E) and -0. 03 mmol/l (M) for HDL-C; -0.13 mmol/l (T), +0.02 mmol/l (E) and -0. 05 mmol/l (M) for LDL-C. Serum triglycerides showed a significant increase during intervention (P < 0.01 by ANOVA) in all groups with a change of 0.18 mmol/l, 0.18 mmol/l and 0.22 mmol/l, for tea, espresso and mocha group respectively. CONCLUSIONS: The results indicate that coffee brewed in the Italian way does not alter blood levels of total cholesterol, HDL-cholesterol and LDL-cholesterol, since no significant differences were observed in these blood parameters after a 6-week break from coffee consumption.     

Female voice communications in high level aircraft cockpit noises--part II: vocoder and automatic speech recognition systems

BACKGROUND: The purpose of the present study was to assess the implications of cholesterol distribution and its change on coronary heart disease (CHD) mortality and disease prevention at a population level. METHODS AND RESULTS: In five independent risk factor surveys (1972, 1977, 1982, 1987, and 1992) in eastern Finland, serum cholesterol was measured in 27721 randomly selected men and women aged 30 to 59 years. The association between cholesterol level and CHD risk and the prediction of the effect of different prevention strategies was estimated by use of logistic regression models. The entire cholesterol distribution of the population shifted markedly toward lower levels between 1972 and 1992. The proportion of subjects with a very high cholesterol level (> or =8.0 mmol/L), also decreased markedly, from 16% to 3%. The risk of CHD death among subjects with cholesterol > or =8.0 mmol/L was approximately 5-fold that of those individuals having cholesterol <5.0 mmol/L. Nevertheless, because CHD risk increases continuously as serum cholesterol increases, and because the number of people having only slightly or moderately increased serum cholesterol was large, most CHD deaths occurred among them. A 10% reduction in cholesterol levels in the entire population would subsequently reduce CHD mortality by 20%, as much as an effective treatment as a 25% decrease in serum cholesterol among all subjects with cholesterol >6.5 mmol/L and four times more than similar treatment of all subjects with cholesterol > or =8.0 mmol/L. CONCLUSIONS: The community-based population strategy in cardiovascular disease prevention was effective in decreasing cholesterol levels among the entire population, including the subjects with the highest cholesterol values. The balanced application of both high-risk and population strategies is needed for the effective prevention of CHD.     

A multicenter study of sleep-wake rhythm disorders: therapeutic effects of vitamin B12, bright light therapy, chronotherapy and hypnotics

OBJECTIVES: To compare the single and joint effect of 1-year diet and exercise intervention on carbohydrate metabolism and associated coronary risk variables. DESIGN: Unmasked, randomized, 2 x 2 factorial intervention trial with 1-year duration for each participant. SETTING: The participants were recruited from a screening examination of 40-year-old persons in Oslo, Norway. SUBJECTS: Two hundred and nineteen sedentary men and women, with diastolic blood pressure 86-99 mmHg, HDL cholesterol < 1.20 mmol L-1, triglycerides > 1.4 mmol L-1, total cholesterol 5.20-7.74 mmol L-1 and BMI > 24. Participants were randomly allocated to control (n = 43), diet (n = 55), exercise (n = 54) and diet+exercise (n = 67). INTERVENTIONS: Exercise: supervised endurance exercise three times a week. Diet: reduce weight, increase the intake of fish and reduce total fat intake. MAIN OUTCOME MEASURES: One-year changes in insulin and glucose before and after a standardized glucose load. RESULTS: As compared with controls fasting insulin in pmol L-1 decreased significantly in the combined diet and exercise group (3.9 +/- 6.2 versus -22.6 +/- 4.7 respectively, P = 0.003). Insulin in pmol L-1 after glucose load decreased significantly in all intervention groups compared to controls (diet: -82.2 +/- 49.9 P = 0.02; exercise: -92.4 +/- 60.1 P = 0.03; diet + exercise: -179.6 +/- 46.1 P = 0.0004). Fasting glucose in mmol L-1 decreased significantly in the diet alone group (0.21 +/- 0.07 P = 0.006) and in the diet+exercise group (-0.26 +/- 0.08 P = 0.005). In a subgroup analysis of the good responders, the observed changes with respect to total cholesterol (-0.76 mmol L-1), HDL cholesterol (0.16 mmol L-1), triglycerides (-0.72 mmol L-1), systolic and diastolic blood pressure (-8.5/ -6.8 mmHg) were all statistically significant compared to the control with P < 0.001). CONCLUSIONS: Exercise and diet intervention and in particular the combination of the two, were effective in improving carbohydrate metabolism. Associated risk factors were also affected in a beneficial direction.     

A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease

Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9,214 men and women from a general population sample and 948 patients with ischemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/liter), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/liter and delta = 0.11 mmol/liter, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischemic heart disease in both genders. On univariate analysis, odds ratios for ischemic heart disease in probands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0.62-1.31), and on multivariate analysis were 1.98 in women (95% CI: 1.11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides not predisposed to ischemic heart disease.     

Long-term clinical follow-up after directional coronary atherectomy

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.     

Apolipoproteins in obesity: effect of weight loss

We evaluated serum concentrations of apoprotein (APO) A1, B, total cholesterol, triglycerides, high density cholesterol (HDL-C), and low density cholesterol (LDL-C) in twelve obese subjects whose body mass index (BMI) was > or = 30 before and after a clinically significant weight loss was obtained utilizing a very-low calorie diet (VLCD) consisting of liquid protein (Optifast) providing 800 calories a day. At baseline, the mean weight +/- SD was 119.77 Kg and decreased significantly to 89.29 +/- 13.46 Kg by 24 weeks. Statistically significant reductions of APO-A1, APO-B, total cholesterol, and triglyceride concentrations were also observed along with the weight loss. LDL-C decreased from 156.0 +/- 55.9 mg/dL to 122.5 +/- 42.2 mg/dL (4.03 +/- 1.4 to 3.16 +/- 1.1 mmol/L), but this difference was not statistically significant. There was no significant change in the HDL-C and the ratios of APO-A1 to APO-B. We conclude that the use of VLCD is associated with changes in the lipid pattern that lower the cardiovascular risk profile in addition to the beneficial effects of weight loss itself.     

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.     

Herpes simplex virus type 1 VP26 is not essential for replication in cell culture but influences production of infectious virus in the nervous system of infected mice

BACKGROUND: The Heart and Estrogen/Progestin Replacement Study (HERS) is the first large clinical trial designed to test the efficacy of postmenopausal estrogen/progestin therapy for secondary prevention of coronary heart disease (CHD). To examine the representativeness of the HERS cohort to the general population of postmenopausal women with CHD, we compared the baseline cardiovascular risk factor data from HERS with similar data from women presumed to have CHD from the National Health and Nutrition Examination Survey (NHANES) III. METHODS: Age, race, and cardiovascular disease risk factors were compared in the 2763 postmenopausal women younger than 80 years old, with a uterus, and with documented CHD in HERS versus 145 similarly aged women with clinical or electrocardiographic evidence of CHD from phase I of NHANES III. RESULTS: There were fewer current smokers in HERS (13%) than in the NHANES cohort (21.7%, p = 0.05). Similarly, a history of hypertension was less prevalent in HERS (58.6%) than in the NHANES cohort (69.3%, p = 0.03). Women with fasting triglyceride levels >3.39 mmol/L or fasting glucose levels >16.6 mmol/L were excluded from HERS, resulting in fewer diabetics (22.9% vs 29.5%, p = 0.26) and lower serum triglyceride levels (1.88 mmol/L vs 2.25 mmol/L, p = 0.19) in HERS versus the NHANES cohort. Systolic and diastolic blood pressure, body mass index, physical activity, and total LDL and HDL cholesterol were not significantly different between the two groups. CONCLUSIONS: The HERS cohort had fewer CHD risk factors than women with myocardial infarction or angina in NHANES III, although comparison is hindered by differences in selection criteria. The many women with diabetes and hypertriglyceridemia in the NHANES cohort emphasizes the importance of testing strategies for secondary prevention of CHD in this high-risk subgroup.     

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.     

Changes in physical activity and health outcomes in a population-based cohort of mid-life Australian-born women

Cross-sectional studies and intervention programs have suggested that physical activity is a potential contributor to the health and wellbeing of mid-life and older women. This prospective longitudinal study investigates whether natural changes in physical activity are associated with changes in health outcomes in a population-based cohort of Australian-born women aged 45-55 years living in Melbourne. Of the 352 women from the Melbourne Women's Midlife Health Project who filled in a base-line physical activity questionnaire, 292 (83 per cent) were evaluated around three years later with regard to physical activity, psychological wellbeing, self-rated health, symptoms experienced, body mass index (BMI), blood pressure and serum lipids. Mean (SD) physical activity measured at base-line was 5.9 (5.7) hours/week, or 1496 (1449) kcal/week; mean (SD) change in physical activity per week was 0.05 (5.24) hours, or 44 (1347) kcal, indicating that although mean change was small there was substantial variation in change. There were significant increases in BMI (P < 0.001), wellbeing (P < 0.05), the number of reported menopause-related symptoms, and high-density lipoprotein cholesterol (HDL-C) levels (P < 0.001), and a decrease in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.05). Change in level of physical activity was positively associated with change in HDL-C (P < 0.01) and change in wellbeing (P = 0.08) and negatively associated with change in coronary heart disease risk score. By increasing physical activity in mid-life, women may reduce at least one risk factor (HDL-C) associated with coronary heart disease.     

Intensity, duration, and frequency of physical activity and coronary risk factors

Relationships between coronary risk factors and intensity, duration, and frequency of leisure activity were studied in 5943 men and 6039 women, ages 25-69. Age, smoking, socioeconomics, season, body mass index (BMI), urbanization, occupational activity, and liquid, alcohol, and saturated/total fat intake were adjusted using multivariate regressions. Among men each 100 kcal.kg-1.wk-1 spent on vigorous activities (7.5-9.0 MET) was associated with: significant (P < 0.01) average differences of -0.36 mmol.L-1 total cholesterol, +0.17 mmol.L-1 HDL cholesterol (P < 0.001), +0.05 HDL/total cholesterol (P < 0.001), -0.33 mmol.L-1 triglycerides, -3 mm Hg diastolic blood pressure, -10 beats.min-1 heart rate (P < 0.001), +30 L.min-1 peak flow, and -1.1 kg.m-2 BMI. Among women it was associated with: -7 mm Hg systolic blood pressure, -6 beats.min-1 heart rate (P < 0.001), +50 L.min-1 peak flow (P < 0.001), and -1.4 kg.m-2 BMI (P < 0.05). Moderate activity (either 3.0-4.5 MET or 5.0-7.0 MET) was significantly (P < 0.05) associated with HDL cholesterol, BMI, and, for men, heart rate; for women, it was associated with HDL/total cholesterol, triglycerides, diastolic blood pressure, and peak flow. With duration and intensity constant, increasing frequency by one time per wk was significantly (P < 0.05) associated with -0.014 mmol.L-1 total cholesterol, +0.001 HDL/total cholesterol, -0.36 beats.min-1 heart rate, -0.093 kg.m-2 BMI among men, and +0.009 mmol.L-1 HDL cholesterol, +0.001 HDL/total cholesterol, -0.014 mmol.L-1 triglycerides, -0.31 beats.min-1 heart rate, and -0.098 kg.m-2 BMI among women. Serum lipids and BMI showed stronger associations with frequency than with intensity or duration.     

Effect of dietary fat reduction and increased aerobic exercise on cardiovascular risk factors

1. The combined effect of dietary fat reduction and increased aerobic exercise on coronary heart disease (CHD) risk factors was investigated in healthy, normolipidaemic, normotensive, sedentary individuals. 2. After a baseline period of 2 weeks, 21 subjects were randomly allocated to one of two intervention groups (low fat exercise (LFEX) or low fat control (LFC)) for 8 weeks. Both groups were counselled to reduce their dietary fat intake to 20-25% energy from fat. The LFEX group was also required to commence an aerobic exercise programme (4 x 45 min per week). 3. In both groups, the falls in total cholesterol seen at week 4 were not maintained at the end of the study; however, the LFEX group maintained a fall in low-density lipoprotein (LDL) of 0.21 +/- 0.11 mmol/L. At the end of the study, the LFC group experienced a fall in high-density lipoprotein (HDL)-cholesterol of 0.16 +/- 0.05 mmol/L, due to a 0.19 +/- 0.07 mmol/L fall in the HDL2 subfraction. The LFEX group experienced no change in HDL (-0.09 +/- 0.06 mmol/L) or HDL2 (-0.09 +/- 0.05 mmol/L). 4. At the end of the study the LFEX and LFC groups experienced a 7 +/- 3 and 5 +/- 1 mmHg fall in systolic blood pressure, respectively, while the LFEX group also observed a 4 +/- 2 mmHg fall in diastolic blood pressure. 5. The benefits of a low-fat diet combined with aerobic exercise include a reduction in LDL and blood pressure, while maintaining HDL through the HDL2 subfraction.     

Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy

BACKGROUND--Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate goal of therapy should be lowering LDL-C or raising HDL-C. METHODS AND RESULTS--Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL-C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0.82+/-0.06 mmol/L (31. 7+/-2.2 mg/dL), versus 1.23+/-0.29 mmol/L (47.4+/-11.2 mg/dL) in patients with baseline HDL-C >/=0.91 mmol/L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin significantly reduced progression among low-HDL-C patients: 0.065+/-0.036 mm versus 0.274+/-0.045 mm in placebo patients (P=0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0. 036+/-0.021 mm and 0.083+/-0.019 mm (P=0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P=0.01); among low-HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. CONCLUSIONS--Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiographic and clinical benefit.