Biomedical subjects
Publications and source records attributed to Lewis H Kuller.
The AIDS epidemic was engrafted on a substantial and rising epidemic of sexually transmitted diseases. Complex social, political, and professional factors are examined through a single risk group to illuminate the initial and continuing failure to combat the epidemic. Selective traditional public health control measures, applied vigorously and creatively within a new legal framework, are still appropriate.
BACKGROUND: The Systolic Hypertension in the Elderly Program (SHEP) demonstrated the benefit of treating isolated systolic hypertension (ISH) in older adults. However, nearly 20% of older adults remain at high risk of heart disease and stroke from untreated ISH. METHODS: For the Pittsburgh SHEP cohort, 11- to 14-year death or cardiovascular event rates were compared for active (n = 135) and placebo (n = 133) arms plus normotensive controls (n = 187). Carotid ultrasound and ankle blood pressures were used to identify subclinical atherosclerosis at baseline. RESULTS: Fourteen-year Kaplan-Meier event rate estimates were 58% vs 79% for the active vs placebo groups (P =.001). Eleven-year event rates for the control, active, and placebo groups were 35%, 47%, and 65%, respectively. Compared with controls, the relative risk of an event was 1.6 (95% confidence interval, 1.1-2.4) for the active treatment group and 3.0 (95% confidence interval, 2.1-4.4) for the placebo group. Baseline history of cardiovascular disease was present in 19% of SHEP participants vs 15% of controls (P =.32), and subclinical disease (carotid stenosis or low ankle blood pressure) was detected in 33% of SHEP participants vs 10% of controls (P<.001). Among those with no clinical or subclinical disease at baseline, the ISH group assigned to active treatment had 10-year event rates similar to those of the control group (29% vs 27%), whereas the placebo rates were much higher (69%). CONCLUSIONS: Treatment of ISH in older adults results in reduced event rates in 14 years. Treatment before advanced atherosclerosis develops will likely produce the best long-term outcome.
OBJECTIVE: This study's objective was to determine if the association between physical activity and lipids and lipoprotein subclasses in postmenopausal women varies by hormone therapy (HT) use. DESIGN: The cross-sectional relationship between physical activity and lipid and lipoprotein subclass relationship was examined before group randomization in 485 postmenopausal (mean age 56.9 [2.9] y) white and African American women from the Woman On the Move through Activity and Nutrition study. This study is a randomized clinical trial designed to test whether a lifestyle intervention will reduce subclinical cardiovascular disease measures. RESULTS: Hormone therapy users (n = 286) were significantly (P < 0.05) younger, less likely to be African American, reported higher levels of physical activity, large very low-density lipoprotein particles (VLDL-P), and medium high-density lipoprotein particles (HDL-P), had a larger mean HDL-P size, and lower levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, small HDL-P, and small VLDL-P than nonusers (n = 196). Physical activity was significantly associated with favorable lipoprotein and lipid levels, regardless of HT use. Some relationships were found to vary significantly by HT use. In nonusers, mean HDL-P and LDL particles (LDL-P) size was significantly larger (P = 0.01 and 0.05, respectively) and total and small LDL-P were significantly lower (both P = 0.02) as activity increased. These relationship were not found in HT users. CONCLUSIONS: Physical activity was significantly related to some lipoprotein subclasses regardless of HT; however, several key lipoprotein subclasses were associated with higher levels of activity only among non-HT users.
OBJECTIVE: The objective of this study was to determine whether psychosocial risk factors for cardiovascular disease (CVD) are associated with impairments in endothelial function and to determine whether use of hormone replacement therapy (HRT) can moderate observed associations among women without prior CVD. METHODS: Flow-mediated dilation was assessed by brachial ultrasound after reactive hyperemia in 193 postmenopausal women enrolled in the prospective Healthy Women Study. Measures of psychosocial characteristics had been completed at study entry, when the women were premenopausal (mean = 13.6 years earlier), and at a separate postmenopausal follow-up exam near the time of the ultrasound (mean = 1.5 years earlier). RESULTS: Factor analyses of the psychosocial characteristics yielded two factors: Type A/anger and anxiety/depression. Anxiety/depression scores at the study entry and follow-up exams and Type A/anger scores at the study entry exam were associated with less vasodilation (p values < 0.05). Type A/anger scores at the follow-up exam were associated with less vasodilation among women not using HRT (p <.05). CONCLUSIONS: Psychosocial risk factors for CVD are associated with impaired brachial artery dilation among postmenopausal women. HRT use may mask some associations between psychosocial risk factors and endothelial dysfunction among postmenopausal women.
UNLABELLED: Marriage confers health benefits for men, but the evidence for women is less consistent. Inconsistent findings may be attributed, in part, to the confounding of marital status and marital quality. OBJECTIVES: The authors examined whether women in satisfying marriages evidence lesser atherosclerosis relative to women in low-satisfying marriages and relative to unmarried women. MATERIALS AND METHODS: Three hundred ninety-three women from the Healthy Women Study participated in this study. Marital status and quality were assessed at baseline when women were premenopausal. Cardiovascular risk factors were also assessed at baseline to determine potential mediators. Markers of atherosclerotic burden--B-Mode ultrasound measures of intima-media thickness and plaque in the carotid arteries and electron beam computed tomography assessments of calcification in the aorta and coronary arteries--were performed, on average, 11 years and 14 years later, respectively. A subset of women underwent a second ultrasound scan approximately 3 years after their first scan. RESULTS: Women in satisfying marriages had the least atherosclerosis in the carotid arteries and aorta, especially relative to those in low-satisfying marriages. Women in satisfying marriages also tended to show less rapid progression of carotid atherosclerosis relative to women in low-satisfying marriages. Women who did not have a partner had intermediate levels of atherosclerosis. Risk factors measured at baseline contributed to the differences between the satisfied and low-satisfied groups, but not those between the satisfied and unmarried groups. CONCLUSIONS: High-quality marriages may protect against cardiovascular disease for women. Studies concerning marriage and cardiovascular health in women should, therefore, concurrently examine marital quality and marital status.
OBJECTIVE: Optimistic people report a higher quality of life, engage in more active coping and adopt more health-promoting behaviors than people low in optimism, ie, pessimism. We evaluated whether pessimists are more likely to show progression in carotid disease than optimists. METHODS: A total of 209 middle-aged healthy premenopausal women enrolled in an epidemiological study of cardiovascular risk factors and had carotid scans 10.4 years and 13.5 years later when they were at least 5 years postmenopausal. Women completed the Life Orientation Test (LOT), a measure of pessimistic and optimistic attitudes, at study entry and at the time of the first carotid scan. Analyses evaluated the association of LOT scores and change in carotid intima medial thickness (IMT) across 3 years. RESULTS: Multiple linear regression analyses showed that the higher the pessimism scores at study entry, the greater the increase in mean IMT (beta = 0.17, p <.007). A comparison of those in the lowest quartile of LOT scores (most optimistic) with those in the other three quartiles showed that the most optimistic group had less progression than the remaining more pessimistic women (mean percent increase = 1.3 and 6.0 for mean IMT, F = 15.4, p <.001). Women who were chronically optimistic at study entry and at the first carotid scan (bottom quartiles at both times) had less progression in mean IMT than did those who were chronically pessimistic (top quartiles at both times). CONCLUSIONS: Optimistic women are less likely to show progression of carotid disease in mid-life than are pessimists.
OBJECTIVE: Hostility may predict coronary heart disease morbidity and mortality, as well as the metabolic syndrome. We tested to see if high levels of the attitudinal and emotional aspects of hostility lead to progression of carotid atherosclerosis in women and if the metabolic syndrome is a mediator of the association. METHODS: Two hundred nine healthy women were followed during the perimenopausal and postmenopausal periods. Carotid artery ultrasound scans measured intima-media thickness (IMT) an average 7.4 (SD = 0.9, range 4.2-10.8) and 10.5 years (SD = 1.1, range = 6.9-13.0) after baseline. Hostility was measured at baseline and at the first carotid scan with Spielberger Trait Anger (being angry frequently) and Anger In (suppressing angry feelings) scales, and the Cook-Medley Hostility Inventory (hostile, cynical attitudes toward others). Metabolic syndrome was measured at the study entry and through the second carotid scan. RESULTS: Baseline Trait Anger scores predicted an increase in IMT across 3 years (p < .05) and predicted the risk for developing the metabolic syndrome (p < .05). The risk for developing the metabolic syndrome, in turn, predicted an increase in IMT across 3 years (p < .05). Anger suppression and cynical attitudes were not associated with progression of carotid atherosclerosis. CONCLUSION: Anger predicts progression of carotid atherosclerosis, and the metabolic syndrome may mediate this association. Women who experience angry feelings frequently may benefit from interventions aimed at reducing anger and reducing the metabolic syndrome components early in the natural history of atherosclerosis.
OBJECTIVE: Reduced cardiac parasympathetic activity, as indicated by a reduced level of clinic or ambulatory high-frequency heart rate variability (HF-HRV), is associated with an increased risk for atherosclerosis and coronary artery disease. We tested whether the reduction in HF-HRV to a psychological stressor relative to a baseline level is also associated with subclinical coronary or aortic atherosclerosis, as assessed by calcification in these vascular regions. METHOD: Spectral estimates of 0.15 to 0.40 Hz HF-HRV were obtained from 94 postmenopausal women (61-69 years) who engaged in a 3-minute speech-preparation stressor after a 6-minute resting baseline. A median of 282 days later, electron beam tomography (EBT) was used to measure the extent of coronary and aortic calcification. RESULTS: In univariate analyses, a greater reduction in HF-HRV from baseline to speech preparation was associated with having more extensive calcification in the coronary arteries (rho = -0.29, p = .03) and in the aorta (rho = -0.22, p = .06). In multivariate analyses that controlled for age, education level, smoking status, hormone therapy use, fasting glucose, high-density lipoproteins, baseline HF-HRV, and the stressor-induced change in respiration rate, a greater stressor-induced reduction in HF-HRV was associated with more calcification in the coronary arteries (B = -1.21, p < .05), and it was marginally associated with more calcification in the aorta (B = -0.92, p = .09). CONCLUSION: In postmenopausal women, a greater reduction in cardiac parasympathetic activity to a psychological stressor from baseline may be an independent correlate of subclinical atherosclerosis, particularly in the coronary arteries.
OBJECTIVE: Negative emotions predict the development of clinical coronary events, and some evidence suggests that negative emotions relate to subclinical atherosclerosis. Low levels of positive emotions and cognitions are relatively unexplored as predictors of cardiovascular risk. We tested the hypothesis that low positive and high negative affect and cognitions would be related to risk for coronary and aortic calcification in healthy women. METHODS: One hundred fifty-five healthy women had measures of positive and negative affect/cognitions obtained before or at the time of electron beam tomography scan of coronary and aortic calcification. RESULTS: Coronary calcification was unrelated to women's psychosocial scores. High aortic calcification was consistently associated with low scores on the Pearlin Mastery Scale and Life Engagement Test and high scores on the CES-Depression Inventory and Negative Interactions Scale in multivariate analyses. Odds ratios (OR [95% confidence intervals (CI)]) from the multivariate binary logistic regression analyses for a SD above the mean scales scores were 0.55 (95% CI, 0.35-0.87) for Pearlin Mastery; 0.56 (95% CI, 0.36-0.86) for the Life Engagement Test; 0.63 (95% CI, 0.40-98) for Life Satisfaction; 1.57 (95% CI, 1.04-2.36) for the CES-Depression; 1.77 (95% CI, 1.15-2.74) for the Cook-Medley Hostility; 1.49 (95% CI, 0.98-2.26) for Spielberger Anger-In; and 2.35 (95% CI, 1.49-3.73) for the Negative Interaction scales. CONCLUSIONS: Women's psychosocial attributes were not related to coronary calcification, raising the possibility that psychosocial attributes are less important for early than late stages of coronary atherosclerosis. The observed associations of psychosocial attributes with aortic calcification may be due to somewhat different risk factors being important for atherosclerosis at different vascular beds. Positive attributes may be related to atherosclerosis and should be studied further.
The recent upsurge in global obesity and the recognition of the role of metabolic syndrome and other correlates of obesity in the etiology of breast cancer and other chronic diseases has created the impetus for renewed interest in the role of anthropometric measures in breast cancer risk. This case-control study was designed to evaluate the role of anthropometric variables in breast cancer susceptibility in an indigenous sub-Saharan African population drawn from midwestern and southeastern Nigeria, a population grossly underreported in the global epidemiologic literature. Study participants were 250 women with breast cancer who were receiving treatment in the surgical outpatient clinics and surgical wards of four university teaching hospitals located in midwestern and southeastern Nigeria, while the controls were 250 age-matched women without breast cancer or other malignant diseases being treated for other surgical diseases in the same institutions between September 2002 and April 2004. Waist:hip ratio (WHR) was associated with a significant 2.5-fold increased risk of premenopausal breast cancer (odds ratio [OR] = 2.56, 95% confidence interval [CI] 1.48-4.41] and a 2-fold increased risk of postmenopausal breast cancer (OR = 2.00, 95% CI 1.04-2.53). Increasing height conferred a modestly nonsignificant increased risk of premenopausal breast cancer (OR = 1.59, 95% CI 0.98-2.58). The study showed that WHR is a significant predictor of breast cancer risk in Nigerian women and measures to sustain increased physical activity and ensure healthy dietary practices are recommended to reduce the burden of obesity in the population.
Knowledge about the epidemiology of subclinical cardiovascular disease (SCVD) in older adults may hold the key for improved opportunities for primary prevention of cardiovascular disease (CVD), a top clinical and public health priority. This review reports findings on the prevalence of SCVD and the ability of SCVD measures to predict incident and adverse outcomes from one of the largest (N=5888) and most comprehensive prospective observational studies on SCVD in older adults, the Cardiovascular Health Study. According to a composite index that combined SCVD measures from different vascular beds, the overall prevalence of SCVD was 37%, making it as common as clinically overt CVD in older adults. SCVD measures strongly predicted incident CVD, stroke, mortality, frailty, and physical and cognitive decline, even after adjustment for traditional CVD risk factors. Ongoing research will address the potential use of SCVD for clinical decision making in older adults.
BACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999. METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD). RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes. CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.
OBJECTIVE: To describe a methodology to evaluate dementia and frequency of different types of dementia and prevalence of the Cardiovascular Health Study (CHS). METHODS: The CHS is a longitudinal study of cardiovascular disease among community-dwelling individuals over the age of 65. Of the 5,888 participants in the original study, 3,608 had a magnetic resonance imaging (MRI) of the brain in 1991, and formed the cohort for the dementia study. The CHS included yearly measures of cognitive function and, from 1998 to 2000, participants were evaluated for dementia by detailed neurological, and neuropsychological examinations. The possible cases of dementia and mild cognitive impairment (MCI) were adjudicated by a review committee of neurologists and psychiatrists. RESULTS: There were 480 cases of (13.3%) incident dementia in the total sample, 227 (6.3%) prevalent dementia, 577 (16.0%) MCI, and 2,318 (64.4%) normal. The adjudication committee classified 69% of the incident dementia as Alzheimer's disease (AD), 11% as vascular dementia (VaD), 16% as both, and 4% as other types. There was a substantial agreement between pre- and postMRI diagnosis of types of dementia. The frequency of dementia within the CHS cohort which survived to the end of the study in 1998-1999, was 13.5% for white men, 14.5% for white women, 22.2% for black men and 23.4% for black women. CONCLUSION: The CHS has developed a methodology for longitudinal studies of dementia in large cohorts and represents the largest study of dementia including cognitive testing, MRI and genetic markers.