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Biomedical subjects

Lewis H Kuller

Publications and source records attributed to Lewis H Kuller.

At least 127 records · Page 7Linked to original sources
PubMed2002

Lipoprotein subclasses and coronary artery calcium in postmenopausal women from the healthy women study.

Lipoprotein subclass levels may improve the prediction of cardiovascular disease (CAD) in individuals beyond the risk assessment provided by conventional enzymatically determined lipid levels. The objective of this study was to evaluate the associations between nuclear magnetic resonance (NMR) spectroscopy-determined lipoprotein subclasses and coronary calcification in postmenopausal women, and to determine whether the associations were independent of conventional lipid measures. Coronary artery calcification (CAC) was measured by electron beam computed tomography, and lipoprotein subclasses were determined by NMR spectroscopy (Liposcience, Inc., Raleigh, NC), in 286 healthy women (mean age = 61.7), at 8 years postmenopause. CAC was analyzed as categories 0, 1 to 99, and > or =100. The mean CAC was 53 (range, 0 to 1,175), and 54% of the women had 0 scores. Large high-density lipoprotein (HDL) was inversely associated with CAC category, but small HDL was not. All very low-density lipoprotein (VLDL) subclasses-small, medium, and large-were positively associated with CAC (p <0.01). Small low-density lipoprotein (LDL) was positively associated with CAC (p <0.01), but medium and large LDL were not. Smaller LDL particle size (p <0.01) and higher levels of LDL particles (p <0.001) were associated with higher CAC category. In separate ordinal logistic regression models, small LDL, LDL particles, and large VLDL were each positively associated (p <0.05) with higher CAC after adjustment for age, systolic blood pressure (SBP), current smoking, and conventional measures of LDL cholesterol, HDL cholesterol, and triglycerides. These results suggest that the measurement of lipoprotein subclasses may improve the prediction of CAD in postmenopausal women beyond that provided by the conventional lipid panel and CAD risk factors.

Adult↗
PubMed2002

Relationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults.

BACKGROUND: In the Cardiovascular Health Study, subclinical cardiovascular disease (CVD) predicted CVD events in older adults. The extent to which this measure or its components reflect calcified coronary disease is unknown. METHODS AND RESULTS: Coronary artery calcium (CAC) was assessed with electron beam tomography in 414 participants without clinical CVD and examined using cut points (CAC> or =400 and CAC> or =800) and the log(CAC); 274 had subclinical CVD by ankle-arm index, ECG, or carotid ultrasound. Cut points for subclinical disease as previously defined in the Cardiovascular Health Study were examined as well as continuous measures to produce receiver operating characteristic curve curves. A low ankle-arm index was highly specific for a high CAC score. The internal carotid artery intima-media thickness was most strongly correlated with CAC (r=0.30) and was significantly related to both CAC cut points and to the log(CAC) score independently of all other measures. CONCLUSIONS: In these community-dwelling older adults without clinical CVD, internal carotid artery intima-media thickness was most closely related to CAC. However, 17.5% of those with a CAC> or =400 would be missed in the ascertainment of subclinical atherosclerosis using the previously published composite of subclinical atherosclerosis. Prospective follow-up will determine whether the CAC score improves prediction of CVD events over other noninvasive measures.

Aged↗
PubMed2002

ELAC2 and prostate cancer risk in Afro-Caribbeans of Tobago.

To test the hypothesis that variation in the putative prostate cancer susceptibility gene ELAC2 contributes to the elevated risk of prostate cancer in Afro-Caribbean males from Tobago, we genotyped the S217L and A514T polymorphisms, previously reported to be associated with prostate cancer risk in a large sample of cases and controls. The frequency of the high-risk Leu allele at the S217L site was the same in cases and controls. Both cases and controls were homozygous for the low-risk Ala allele at the A514T site. In addition, we sequenced the exons and 3'- and 5'-flanking regions of ELAC2 in 24 individuals with histologically confirmed prostate cancer. We identified 17 new single nucleotide polymorphisms. An A(-1196)T polymorphism, which alters a predicted TATA box consensus sequence, was tested in cases and controls, and no significant difference in allele or genotype frequencies was observed. The absence of ELAC2 mutations and lack of association between polymorphisms in ELAC2 and prostate cancer in cases and controls leads us to conclude that ELAC2 does not contribute significantly to the elevated prevalence of prostate cancer in Afro-Caribbean males of Tobago.

Adult↗
PubMed2002

Racial differences in coronary artery calcification in older adults.

Reports on race-related differences in coronary artery calcium (CAC) are just beginning to emerge and have not been well studied in the elderly. This study was undertaken to assess whether such differences exist and the relationship between CAC and cardiovascular risk factors in a cohort of elderly community-dwelling adults. CAC was measured by using electron-beam tomography in 614 adults (aged 67 to 99 years), of whom 59% were women and 23% were black. The median CAC score was lower in blacks than in whites for men (159 versus 787, respectively; P<0.001) and for women (134 versus 233, respectively; P=0.02) after adjustment for age, cardiovascular disease, and risk factors for cardiovascular disease, although this difference was stronger and remained significant among men only. Lower CAC scores were also observed in the subgroup of blacks with a history of myocardial infarction. The lower CAC scores in blacks compared with whites observed in this study is consistent with either a lower prevalence of coronary artery disease or a lower extent of calcification of coronary artery disease.

Age Factors↗
PubMed2002

Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study.

BACKGROUND: The contributions of fasting and 2-hour postchallenge glucose level to cardiovascular events remain ill-defined, especially for nondiabetic adults. This study examined the relative predictive power of fasting and 2-hour glucose level on cardiovascular event risk. METHODS: A total of 4014 community-dwelling adults 65 years or older who participated in the baseline visit of the Cardiovascular Health Study and who were without treated diabetes or previous myocardial infarction or stroke were eligible for analyses. Participants with treated diabetes at baseline were excluded. Incident myocardial infarction or stroke, or coronary death, was the outcome of interest. Age-, sex-, and race-adjusted proportional hazards regression models described individual and joint associations between baseline measures of fasting and 2-hour postchallenge glucose level and event risk. RESULTS: There were 764 incident cardiovascular events during 8.5 years of follow-up. Fasting glucose level of 115 mg/dL (6.4 mmol/L) or more was associated with an increased cardiovascular risk (hazard ratio [HR], 1.66 [95% confidence interval (CI), 1.39-1.98]) in adjusted analyses compared with fasting glucose level less than 115 mg/dL. Two-hour glucose level was associated with a linear risk (HR, 1.02 [95% CI, 1.00-1.04] per 10 mg/dL [0.6 mmol/L]) that included an additional increase in risk for 2-hour glucose level of 154 mg/dL (8.5 mmol/L) or more (HR, 1.29 [95% CI, 1.04-1.59]) in adjusted analyses. In joint fasting and 2-hour glucose models, only 2-hour glucose level remained predictive of event risk. CONCLUSIONS: Two-hour glucose level was better than fasting glucose level alone at identifying older adults at increased risk of major incident cardiovascular events.

Aged↗
PubMed2002

Subclinical atherosclerosis in multiple vascular beds: an index of atherosclerotic burden evaluated in postmenopausal women.

The Healthy Women Study has evaluated risk factor changes as women go through the menopause. In 274 women, measures of atherosclerosis in the coronary, aorta and carotid arteries were obtained at 8 years postmenopause using electron beam tomography and carotid ultrasound. The purpose of this study was to evaluate the association between baseline premenopausal risk factors and subclinical disease in various vascular beds and with an aggregate atherosclerosis index based on all subclinical measures. The prevalence of measurable disease for the coronaries, carotids and aorta was 45, 55 and 72%, respectively. Disease measures across these three locations were significantly correlated (P<0.001). Premenopausal LDL, triglycerides, blood pressure (BP) and smoking were associated with each measure of subclinical atherosclerosis, and were strikingly associated with the number of elevated disease measures. Among 126 women taking hormone replacement therapy (HRT), there was a strong positive association between systolic BP and subclinical atherosclerosis (P<0.001). No such relationship was seen among women not on HRT and this interaction was significant (P=0.048). An index of subclinical atherosclerosis rather than measurement at a single arterial site may be the best estimate of disease risk. Such a measure should be evaluated for its prognostic value along with individual measures of subclinical disease. Women with lower premenopausal risk factors did not develop high levels of subclinical atherosclerosis, suggesting that atherosclerosis is a preventable disease in women.

Adult↗
PubMed2002

Correlates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study.

BACKGROUND: Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals. METHODS: Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998. RESULTS: Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993. CONCLUSIONS: In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima-media thickness, heart rate, and decreased physical activity measured several years earlier.

Aged↗
PubMed2002

Glucose, blood pressure, and lipid control in older people with and without diabetes mellitus: the Cardiovascular Health Study.

OBJECTIVES: To determine the prevalence of cardiovascular risk-factor treatment and control in older adults with normal fasting glucose, impaired fasting glucose, and diabetes mellitus and whether those with diabetes mellitus had better risk factor control than older adults with normal fasting glucose. DESIGN: Secondary analysis of data from population-based, prospective cohort study of risk factors for cardio-vascular and cerebrovascular disease in older people (Cardiovascular Health Study). SETTING: Community-based. PARTICIPANTS: Community-dwelling adults aged 65 and older. MEASUREMENTS: Fasting plasma glucose, serum cholesterol and its subfractions, systolic and diastolic blood pressures, and body mass index. RESULTS: There were 579 (18%) cohort members with diabetes mellitus (77% receiving antidiabetic medication, 23% with fasting glucose > or =126 mg/dL and no treatment), 213 (6%) with impaired fasting glucose, and 2,582 (77%)with normal fasting glucose. Of diabetic participants, 12% had recommended fasting glucose levels of less than 110 mg/dL. Of participants with hypertension, a larger proportion of diabetic participants than nondiabetic participants (89% versus 75%, P < .01) was treated with antihypertensive agents, but a smaller proportion of diabetic participants had recommended blood pressure levels of 129/85 mmHg or lower than nondiabetic participants had recommended blood pressure levels of 139/89 mmHg or lower (27% vs 48%, P < .01). Diabetic dyslipidemic participants were treated less often with lipid-lowering therapy (26% versus 55%, P < .01) and achieved recommended low-density lipoprotein goals less often (8%versus 54%, P < .01) than nondiabetic dyslipidemic participants. CONCLUSIONS: Overall, treatment and control of cardiovascular risk factors were suboptimal in this older population, especially among those with diabetes mellitus. Optimizing risk-factor control can improve health outcomes in older adults with and without diabetes mellitus.

Age Factors↗
PubMed2002

The relationship between psychological risk attributes and the metabolic syndrome in healthy women: antecedent or consequence?

The metabolic syndrome is an important risk factor for major chronic diseases in women. A key component of the syndrome, central adiposity, is correlated with psychological risk factors associated with coronary artery disease in prior epidemiological studies. We evaluated if psychological risk factors predicted the metabolic syndrome and if the metabolic syndrome predicted psychological distress. A population-based cohort of 425 women who were middle-aged, and pre-, peri-, and postmenopausal was followed for an average 7.4 years. Psychological risk factors, including depression, anxiety, tension, current perceived stress, and anger, and biological components of the metabolic syndrome, including glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, waist circumference, and blood pressure (BP) were measured at baseline and at examinations 1 to 8 years postmenopause. Women were classified according to the National Heart, Lung, and Blood Institute (NHLBI) criteria for metabolic syndrome. Women who exhibited high levels of depression, tension, and anger at baseline, and increased in anger during the follow-up had elevated risk for developing the metabolic syndrome during follow-up, P <.04. The metabolic syndrome at baseline, in turn, predicted increasing anger and anxiety 7.4 years later, P <.001. Psychological risk factors affect the development of the metabolic syndrome. The association between anger and the metabolic syndrome is reciprocal. Reduction in the level of psychological distress may prevent the development of the metabolic syndrome in women.

Adult↗
PubMed2002

A community-based study of postmenopausal white women with back and leg pain: health status and limitations in physical activity.

BACKGROUND: The objective of this study was to determine the prevalence of lower back pain and associated leg pain/numbness in postmenopausal Caucasian women and the relationship of these symptoms to health status and function. METHODS: A convenience sample of 573 white women enrolled in the Observational Study of the Women's Health Initiative (WHI) in Pittsburgh completed a questionnaire on low back pain (LBP) and leg pain (LP) and its impact on their daily activity. For data analysis, this information was merged with that obtained under the standard WHI protocol. RESULTS: Almost half of the women (49%) reported having had LBP during the previous month: 8% had LBP only, while 41% had both LBP and LP. In 9% of women, the leg and back symptoms were alleviated by sitting. Among women with LBP during the previous month, those who also had leg pain were five times more likely to have had functional limitations, two to four times more likely to have consulted a clinician or taken medications, and more likely to have had prior spinal surgery or hospitalization than the women with no LP. Based on the Short Form-36, women with LBP/LP had significantly lower scores for physical function, physical role, and bodily pain than women with no LBP or with LBP alone. CONCLUSIONS: Low back pain that radiates into the hip, buttock, or leg is relatively common in postmenopausal Caucasian women living in the community and is associated with decreased physical health status and with physical limitations.

Activities of Daily Living↗
PubMed2002

The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study.

AIMS: To describe the association of retinopathy with atherosclerosis and atherosclerotic risk factors in people with diabetes. METHODS: 296 of the 558 people classified as having diabetes by the American Diabetes Association criteria, from a population based cohort of adults (ranging in age from 69 to 102 years) living in four United States communities (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were studied from 1997 to 1998. Lesions typical of diabetic retinopathy were determined by grading a 45 degrees colour fundus photograph of one eye of each participant, using a modification of the Airlie House classification system. RESULTS: Retinopathy was present in 20% of the diabetic cohort, with the lowest prevalence (16%), in those 80 years of age or older. Retinopathy was detected in 20.3% of the 296 people with diabetes; 2.7% of the 296 had signs of proliferative retinopathy and 2.1% had signs of macular oedema. The prevalence of diabetic retinopathy was higher in black people (35.4%) than white (16.0%). Controlling for age, sex, and blood glucose, retinopathy was more frequent in black people than white (odds ratio (OR) 2.26, 95% confidence interval (CI) 1.01, 5.05), in those with longer duration of diabetes (OR (per 5 years of diabetes) 1.42, 95% CI 1.18, 1.70), in those with subclinical cardiovascular disease (OR 1.49, 95% CI 0.51, 4.31), or coronary heart disease or stroke (OR 3.23, 95% CI 1.09, 9.56) than those without those diseases, in those with higher plasma low density lipoprotein (LDL) cholesterol (OR (per 10 mg/dl of LDL cholesterol) 1.12, 95% CI 1.02, 1.23), and in those with gross proteinuria (OR 4.76, 95% CI 1.53, 14.86). CONCLUSION: Data from this population based study suggest a higher prevalence of retinopathy in black people than white people with diabetes and the association of cardiovascular disease, elevated plasma LDL cholesterol, and gross proteinuria with diabetic retinopathy. However, any conclusions or explanations regarding associations described here must be made with caution because only about one half of those with diabetes mellitus were evaluated.

Age of Onset↗
PubMed2002

Achieving and maintaining cognitive vitality with aging.

Cognitive vitality is essential to quality of life and survival in old age. With normal aging, cognitive changes such as slowed speed of processing are common, but there is substantial interindividual variability, and cognitive decline is clearly not inevitable. In this review, we focus on recent research investigating the association of various lifestyle factors and medical comorbidities with cognitive aging. Most of these factors are potentially modifiable or manageable, and some are protective. For example, animal and human studies suggest that lifelong learning, mental and physical exercise, continuing social engagement, stress reduction, and proper nutrition may be important factors in promoting cognitive vitality in aging. Manageable medical comorbidities, such as diabetes, hypertension, and hyperlipidemia, also contribute to cognitive decline in older persons. Other comorbidities such as smoking and excess alcohol intake may contribute to cognitive decline, and avoiding these activities may promote cognitive vitality in aging. Various therapeutics, including cognitive enhancers and protective agents such as antioxidants and anti-inflammatories, may eventually prove useful as adjuncts for the prevention and treatment of cognitive decline with aging. The data presented in this review should interest physicians who provide preventive care management to middle-aged and older individuals who seek to maintain cognitive vitality with aging.

Aging↗
PubMed2002

Lack of association between adipose tissue distribution and IGF-1 and IGFBP-3 in men and women.

Insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and obesity, and in particular visceral obesity, are putative cancer risk factors. Little is known, however, about the relationship between IGFs and obesity. We investigated the relationship between adipose tissue distribution and IGF-1 and IGFBP-3. Single-slice abdominal computed tomography scanning through the L4-L5 interspace was used to measure visceral adipose tissue (VAT) and subcutaneous adipose tissue (SQAT) in 432 community-based subjects (267 men, 165 women; ages, 55-77), participating in a cancer screening trial. Insulin, IGF-1, IGFBP-3, and the ratio of IGF-1:IGFBP-3, measured by radioimmunoassay, were compared with age, body mass index, absolute and relative VAT and SQAT, and total abdominal fat. We found that men had a higher mean IGF-1 (129.5 versus 108.9 ng/ml; P < 0.0001) and more VAT (201.5 cm(3) versus 166.6 cm(3); P < 0.0001) than women. In men and women, there was no correlation between IGF-1, IGFBP-3, or the ratio of IGF-1:IGFBP-3 with body mass index, total fat, VAT or SQAT, or fasting insulin. In contrast, fasting insulin was highly correlated to all measures of obesity (P = 0.0001). We conclude that obesity, adipose tissue distribution, and in particular VAT are not correlated with IGF-1, IGFBP-3, or the molar ratio of IGF-1:IGFBP-3. The lack of association between obesity and the IGF-1 axis suggests that the IGF-1 axis is not a likely mediator between VAT and disease.

Adipose Tissue↗
PubMed2002

High prevalence of screening-detected prostate cancer among Afro-Caribbeans: the Tobago Prostate Cancer Survey.

Risk for prostate cancer is high among African Americans. We hypothesized that risk for prostate cancer is also high in other populations of African descent. Our objective was to determine the screening-detected prevalence of prostate cancer in the predominantly Afro-Caribbean population on the island of Tobago. Male residents, ages 40-79 years, were invited to participate in a population-based screening for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal exam (DRE). Men with elevated PSA (>or=4 ng/ml) or abnormal DRE were offered an ultrasound-guided sextant biopsy of the prostate gland. Men (2484), ages 40-79 years, underwent prostate cancer screening between September 1997 and June 2001. Mean age was 55.9, SD was 10.6 years, and median was 54 years. Mean serum PSA was 14.8 ng/ml, SD was 376 [excluding 4 values >or= 2 SD above the mean (1,112, 1,317, 1,818, and 18,330 ng/ml) mean PSA was 5.5 ng/ml and SD was 29.6], and median PSA was 1.2 ng/ml. Elevated PSA and/or abnormal DRE were observed in 31% (759 of 2484) overall, and in age groups 40-49 (87 of 843, 10%), 50-59 (201 of 729, 28%), 60-69 (262 of 584, 45%), and 70-79 (209 of 328, 64%). Of 681 men biopsied, 259 (38%, or 10% of the 2484 screened) were diagnosed with prostate cancer. Age-specific rates of screening detected prostate cancer were: 1%, ages 40-79 years; 7%, ages 50-59 years; 18%, ages 60-69 years; and 28%, ages 70-79 years. These screening results indicate a very high screening-detected prevalence of prostate cancer in this population of West African descent. These data support the hypothesis that populations of African descent share genetic and/or lifestyle factors that contribute to their elevated risk for prostate cancer.

Adult↗