A time to stop prescribing antioxidant vitamins to prevent and treat heart disease?
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Biomedical subjects
Publications and source records attributed to L H Kuller.
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The aim of the study was to test the hypotheses that the trajectory of psychological risk (ie, persistent or increasing measures of depression and anxiety symptoms, anger, and low social support over time) increases the risk for the development of hypertension and that blood pressure levels fluctuate with psychological changes in women. Initially, healthy normotensive middle-aged women (n=541; 90.6% white, 8.9% African American) were followed across an average of 9.2 years of follow-up. Psychological characteristics were assessed repeatedly via standardized questionnaires, and Cox proportional hazards and random regression models were used to analyze their impact, adjusting for hypertension risk factors (age, race, years of education, parental history of hypertension, baseline blood pressure, body mass index, physical activity, alcohol use, and cigarette smoking). Seventy-five women became hypertensive during the follow-up period. Baseline levels of depression, anxiety, anger, and social support did not predict subsequent hypertension. A high level of anxiety throughout the follow-up, an increase in the level of feelings of anger, and a decrease in the level of social support over the follow-up were significant predictors of hypertension incidence (all P<0.05), although covariate adjustment reduced some of the significance levels to nonsignificance. In women, increases in depressive symptoms were significantly associated (P=0.003) with concurrent increases in the level of systolic blood pressure, especially among hypertensive patients (P=0.0001). Increasing levels of anger, decreasing levels of social support, and high anxiety increase the likelihood of women's development of hypertension in midlife. These results emphasize the importance of evaluating the trajectory of psychological risk during the period of evolving hypertension.
The determinants of blood levels of estrogen, estrogen metabolites, and relation to receptors and post-transitional effects are the likely primary cause of breast cancer. Very high risk women for breast cancer can now be identified by measuring bone mineral density and hormone levels. These high risk women have rates of breast cancer similar to risk of myocardial infarction. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporotic fracture, and breast cancer. The potential intervention of hormone replacement therapy, obesity, or weight gain and increased atherogenic lipoproteinemia may be of concern and confound the results of clinical trials. Estrogens, clearly, are important in the risk of bone loss and osteoporotic fracture. Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone loss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, higher dose of calcium or vitamin D, or use of bone reabsorption drugs in coordination with weight loss should be evaluated. Any therapy that raises blood estrogen or metabolite activity and decreases bone loss may increase risk of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid intimal medial thickness and plaque, endothelial function, breast density, hormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies.
BACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy. METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (</=1:512), high-titer (1:1024) C pneumoniae antibody was associated with an increased risk (OR 2.2, 95% CI 1.1 to 4.4). CONCLUSIONS: Among older adults, the presence of IgG antibodies to HSV-1 was associated with a 2-fold increase in the risk of incident MI and CHD death. For C pneumoniae, only high-titer IgG antibodies were associated with an increased risk of MI and CHD death. The presence of IgG antibodies to CMV was not associated with risk among the elderly.
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OBJECTIVES: We sought to examine the relationship between reproductive history and measures of selected gonadotrophins and steroid hormones among post-menopausal women. Previous studies have suggested that there is a negative correlation between parity and post-menopausal serum estrogens, which may be a mechanism by which pregnancies protect women from the development of breast cancer. METHODS: We analyzed women who experienced a natural menopause within the Healthy Women Study cohort both 1 and 8 years after menopause. Lifetime reproductive history was obtained and blood was assayed for estrone, estradiol, androstenedione, testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) at 1 year post-menopause and for many of these steroid hormones at 8 years post-menopause. Also at 8 years post-menopause, a hip bone mineral density measure was obtained. RESULTS: Age at menopause related to a modest increase in estrone at 1 year but a decrease in estrone and estradiol at eight years. Adjustment for body mass index (BMI), oral contraceptive use, alcohol use, cigarette smoking, and education had little impact on these findings. There were no other internally consistent relationships between reproductive variables and steroid hormones or hip-bone mineral density. CONCLUSIONS: These observations do not support the hypothesis that parity acts to diminish endogenous levels of post-menopausal estrogens.
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In the Type 1 diabetes population, coronary heart disease (CHD) and lower-extremity arterial disease (LEAD) are the two common macrovascular complications leading to early mortality and morbidity. However, it is not clear if these two complications share the same risk factors. The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study prospectively examined and compared the risk factors for LEAD and CHD (including CHD morbidity and mortality). EDC subjects (332 men and 325 women), all diagnosed at Children's Hospital of Pittsburgh between 1950 and 1980, were first examined at baseline (1986-1988), and then biennially, for diabetes complications and their risk factors. Data used in the current analysis were from the first 6 years of follow-up, 98% provided at least some follow-up data for these analyses. CHD was defined as the presence of angina (diagnosed by the EDC examining physician) or a history of confirmed myocardial infarction or CHD death. An ankle-to-arm ratio of less than 0.9 at rest was considered to be evidence of LEAD. Among 635 subjects without CHD at baseline, 57 developed CHD (1.69/100 person-years), and among 579 without LEAD at baseline, 70 developed LEAD (2.31/100 person-years). CHD incidence rate was slightly higher in males, while LEAD incidence rate was slightly higher in females. Compared to non-incident cases, subjects who developed either complication were older, had a longer diabetes duration, higher LDL and total cholesterol, and were more likely to be hypertensive. In multivariate analyses, hypertension, low HDL cholesterol level, high white cell count, depression, and nephropathy were the independent risk factors for CHD (including morbidity and mortality). For LEAD, higher HbA1 level, higher LDL cholesterol level and smoking were the important contributing factors. In conclusion, the risk factor patterns differ between the two vascular complications. Glycemic control does not predict CHD overall but does predict LEAD, while hypertension and inflammatory markers are more closely related to CHD than to LEAD.
Hormone replacement therapy is extensively used in the United States, especially for the possible prevention of heart disease, osteoporotic fractures, and, more recently, dementia. The results of recent clinical trials have raised new questions about the risk and benefits of estrogen or estrogen/progesterone therapy to prevent heart attacks, the choice of specific drug therapy such as specialized estrogen receptor modulation (SERM). The change in risk factors, especially weight gain or obesity, may determine the risks and benefits of hormone replacement therapy.
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Coronary heart disease (CHD) is the leading cause of death for women in the United States. There has been a substantial decrease in CHD mortality in the past few decades in the United States for both women and men. The change in lifestyle after World War II may affect the incidence of and mortality from CHD in a more recent birth cohort, such as the 45-54-year-old age group. CHD mortality among women aged 45-54 by state and race in the United States and other countries in 1994 was evaluated. Correlation of the CHD mortality with state-specific and race-specific educational attainment (% of not a high school graduate) and state-specific prevalence of smoking was examined. There was a 2.5-fold difference in CHD mortality (ICD 410-414, 429.2) between black and white women aged 45-54: 78/100,000 for black versus 31/100,000 for white women; a 3-fold difference in CHD mortality among white women by state: 16/100,000 in Colorado versus 53/100,000 in Louisiana; and a 3-fold difference in CHD mortality among black women by state: 45/100,000 in New Jersey versus 124/100,000 in Arkansas. CHD mortality was correlated with educational attainment among white women (r = 0.62, p = 0.001) and with prevalence of smoking (r = 0.39, p = 0.021). There is a large variation in CHD mortality among women aged 45-54 in the United States by race and state. These differences may reflect variations in coronary risk factors. More detailed evaluation of determinants of CHD mortality by area is needed, as are public health programs that can reduce the marked disparity in CHD mortality in the United States.
BACKGROUND: The amount of calcium ingested by an individual may affect several chronic conditions, including osteoporosis, hypertension, and colon cancer. However, individuals vary in their ability to absorb the calcium they consume. OBJECTIVE: The purpose of this study was to examine sources of interindividual variation in the efficiency of calcium absorption in women. DESIGN: Fractional calcium absorption was estimated in 142 healthy pre- and perimenopausal women. Dietary habits, lifestyle factors, calciotropic hormones, and vitamin D receptor gene polymorphisms were also assessed. RESULTS: Calcium absorption values averaged 35% and ranged from 17% to 58%. Fractional calcium absorption was positively associated with body mass index (r = 0.22, P = 0.007), dietary fat intake (r = 0.29, P = 0.001), serum 1,25 dihydroxyvitamin D [1,25(OH)(2)D] concentrations (r = 0.23, P = 0. 006), and parathyroid hormone concentrations (r = 0.21, P = 0.015). Fractional calcium absorption was inversely associated with total calcium intake (r = -0.18, P = 0.030), dietary fiber intake (r = -0. 19, P = 0.028), alcohol consumption (r = -0.14, P = 0.094), physical activity (r = -0.22, P = 0.007), and symptoms of constipation (r = -0.16, P = 0.059). In stepwise regression analysis, dietary fat, dietary fiber, serum 1,25(OH)(2)D, and alcohol consumption emerged as independent predictors of calcium absorption, explaining 21.02% of the observed variation. Women in the lowest tertile of the ratio of dietary fat to fiber had 19% lower fractional calcium absorption values than did women in the highest tertile of ratio of dietary fat to fiber (test of trend, P < 0.001). CONCLUSIONS: There is a wide range of calcium absorption values in healthy women. The amount of dietary fat consumed relative to dietary fiber appears to have an important role in determining differences in calcium absorption performance among individuals.
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BACKGROUND: Coronary artery calcification (CAC) reflects the extent of coronary artery atherosclerosis. The extent of coronary artery calcification is not well described in older adults. OBJECTIVE: To determine the extent of CAC in older adults participating in a large population study of cardiovascular disease (CVD), especially those characterized as having minimal clinical or subclinical cardiovascular disease. DESIGN: An observational epidemiologic study. POPULATION: Participants in the Cardiovascular Health Study Cohort, mean age 78 years, who had electron beam computed tomography (EBT) scan of the heart (n = 133); included were 106 persons with no prior evidence of clinical or subclinical CVD. MEASUREMENTS: Total CAC score was measured using cardiac EBT. Cardiovascular disease and risk factors, as well as carotid ultrasound, electrocardiogram, echocardiogram, and ankle-arm index, had been measured previously to define subclinical disease. Previous cerebral magnetic resonance imaging was also evaluated. RESULTS: Overall, the CAC scores were higher in those with clinical cardiovascular disease or evidence of subclinical cardiovascular disease than in those with no evidence of disease. For the 106 participants without evidence of clinical or subclinical disease, the median score was 176, compared with 367 in those with subclinical disease and 923 in those with clinical CVD. Seventeen persons had scores of zero. There was little difference in risk factors across quartiles of CAC in the subgroup of 106 with prior characterization of minimal CVD despite the broad range of CAC scores. There was a higher proportion of those with white matter grade > or = 2 by magnetic resonance imaging among those with higher CAC scores (P = .025). Infarct-like lesions prevalence ranged from 12.5% in the lowest group to 47.1% in the highest CAC group (P = .019). CONCLUSIONS: Older adults with evidence of clinical or subclinical CVD have higher total CAC scores. Though the extent of coronary artery calcification was lower in those with minimal evidence of CVD, the range was broad and not explained by CVD risk factors.
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. An adverse lipid profile has also been observed in PCOS-affected women, suggesting that these individuals may be at increased risk for coronary heart disease at a young age. The objective of the present study was to evaluate subclinical atherosclerosis among women with PCOS and age-matched control subjects. A total of 125 white PCOS cases and 142 controls, aged >/=30 years were recruited. Collection of baseline sociodemographic data, reproductive hormone levels, and cardiovascular risk factors was conducted from 1992 to 1994. During follow-up (1996 to 1999), these women underwent B-mode ultrasonography of the carotid arteries for the evaluation of carotid intima-media wall thickness (IMT) and the prevalence of plaque. A significant difference was observed in the distribution of carotid plaque among PCOS cases compared with controls: 7.2% (9 of 125) of PCOS cases had a plaque index of >/=3 compared with 0.7% (1 of 142) of similarly aged controls (P=0.05). Overall and in the group aged 30 to 44 years, no difference was noted in mean carotid IMT between PCOS cases and controls. Among women aged >/=45 years, PCOS cases had significantly greater mean IMT than did control women (0.78+/-0.03 versus 0.70+/-0.01 mm, P:=0. 005). This difference remained significant after adjustment for age and BMI (P:<0.05). These results suggest that (1) lifelong exposure to an adverse cardiovascular risk profile in women with PCOS may lead to premature atherosclerosis, and (2) the PCOS-IMT association is explained in part by weight and fat distribution and associated risk factors. There may be an independent effect of PCOS unexplained by the above variables that is related to the hormonal dysregulation of this condition.