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Biomedical subjects

Lewis H Kuller

Publications and source records attributed to Lewis H Kuller.

At least 55 records · Page 3Linked to original sources
PubMed2006

Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study.

OBJECTIVE: The objective of this study was to assess the association of inflammation with hyperglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT]) and diabetes in older individuals. RESEARCH DESIGN AND METHODS: Baseline data from the Health, Aging and Body Composition study included 3,075 well-functioning black and white participants, aged 70-79 years. RESULTS: Of the participants, 24% had diabetes and 29% had IFG/IGT at baseline. C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels (P < 0.001) were significantly higher among diabetic participants and those with IFG/IGT. Odds of elevated IL-6 and TNF-alpha (>75th percentile) were, respectively, 1.95 (95% CI 1.56-2.44) and 1.88 (1.51-2.35) for diabetic participants and 1.51 (1.21-1.87) and 1.14 (0.92-1.42) for those with IFG/IGT after adjustment for age, sex, race, smoking, alcohol intake, education, and study site. Odds ratios for elevated CRP were 2.90 (2.13-3.95) and 1.45 (1.03-2.04) for diabetic women and men and 1.33 (1.07-1.69) for those with IFG/IGT regardless of sex. After adjustment for obesity, fat distribution, and inflammation-related conditions, IL-6 remained significantly related to both diabetes and IFG/IGT. CRP in women and TNF-alpha in both sexes were significantly related to diabetes, respectively, whereas risk estimates for IFG/IGT were decreased by adjustment for adiposity. Among diabetic participants, higher levels of HbA(1c) were associated with higher levels of all three markers of inflammation, but only CRP remained significant after full adjustment. CONCLUSIONS: Our findings show that dysglycemia is associated with inflammation, and this relationship, although consistent in diabetic individuals, also extends to those with IFG/IGT.

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PubMed2006

Effect of weight loss and nutritional intervention on arterial stiffness in type 2 diabetes.

OBJECTIVE: There is increased stiffness of the large central arteries in type 2 diabetic patients, and obesity is a risk factor. However, the effect of intentional weight loss on arterial stiffness is uncertain, and the purpose of the current study was to assess this effect. RESEARCH DESIGN AND METHODS: Arterial stiffness was assessed by measuring aortic pulse wave velocity (aPWV) at baseline and at completion of a 1-year weight loss intervention. Metabolic control of type 2 diabetes was also appraised. RESULTS: Mean weight loss at 1 year in 38 volunteers with type 2 diabetes was 7.8%. There were improvements in HbA1c, LDL cholesterol, homeostasis model assessment of insulin resistance, and inflammatory markers (plasminogen activator inhibitor-1, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein). There was also a significant improvement in aPWV at completion of weight loss intervention, from 740 to 690 cm/s (P < 0.05). CONCLUSIONS: Moderate weight loss improves arterial stiffness in type 2 diabetes.

Adult↗
PubMed2006

Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial.

OBJECTIVE: To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: A total of 10,950 Multiple Risk Factor Intervention Trial (MRFIT) survivors were followed for mortality an additional median 18.4 years (1980-1999). Proportional hazards models examined multivariate-adjusted risks associated with Adult Treatment Panel III-defined metabolic syndrome conditions, with BMI substituted for waist circumference. RESULTS: At MRFIT annual visit 6, 4,588 (41.9%) men, mean age (+/-SD) 53.0 +/- 5.9 years, had metabolic syndrome and 6,362 did not. Comparing men with metabolic syndrome to men without, adjusted hazard ratios (HRs) were 1.21 (95% CI 1.13-1.29), 1.49 (1.35-1.64), and 1.51 (1.34-1.70) for 18-year total, CVD, and coronary heart disease mortality, respectively. Among men with metabolic syndrome, elevated glucose (1.54 [1.34-1.78]) and low HDL cholesterol (1.45 [1.17-1.54]) were most predictive of CVD mortality, followed by elevated BMI (1.34 [1.17-1.54]), elevated blood pressure (1.25 [0.98-1.58]), and elevated triglycerides (1.06 [0.86-1.30]). In contrast, for men without metabolic syndrome, the HR for low HDL cholesterol was 1.02 (0.86-1.22). Among metabolic syndrome men with no nonfatal CVD event, smokers with elevated LDL cholesterol showed higher CVD mortality (1.79 [1.22-2.63]) compared with nonsmokers without elevated LDL cholesterol; this additional risk was even greater for metabolic syndrome men with a nonfatal CVD event (2.11 [1.32-3.38]). CONCLUSIONS: Metabolic syndrome is associated with an increased risk of mortality. Among those with metabolic syndrome, risk is further increased by having more metabolic syndrome conditions, by cigarette smoking, and by elevated LDL cholesterol. Primary prevention of each metabolic syndrome condition should be emphasized, and presence of each condition should be treated in accordance with current guidelines.

Body Mass Index↗
PubMed2005

Breast cancer risk factors and mammographic breast density in women over age 70.

BACKGROUND: Breast density is a strong risk factor for breast cancer, but little is known about factors associated with breast density in women over 70. METHODS: Percent breast density, sex hormone levels and breast cancer risk factor data were obtained on 239 women ages 70-92 recruited from 1986 to 1988 in the United States. Multivariable linear regression was used to develop a model to describe factors associated with percent density. RESULTS: Median (range) percent density among women was 23.7% (0-85%). Body mass index (beta=-0.345, p<0.001 adjusted for age and parity) and parity (beta=-0.277, p<0.001 adjusted for age and BMI) were significantly and inversely associated with percent breast density. After adjusting for parity and BMI, age was not associated with breast density (beta=0.05, p=0.45). Parous women had lower percent density than nulliparous women (23.7 versus 34.7%, p=0.005). Women who had undergone surgical menopause had greater breast density than those who had had a natural menopause (33.4 versus 24.8%, p=0.048), as did women who were not current smokers (26.0 versus 17.3% for smokers, p=0.02). Breast density was not associated with age at menarche, age at menopause, age at first birth, breastfeeding, estrogen levels or androgen levels. In a multivariable model, 24% of the variance in percent breast density was explained by BMI (beta=-0.35), parity (beta=-0.29), surgical menopause (beta=0.13) and current smoking (beta=-0.12). CONCLUSION: Factors associated with breast density in older, post-menopausal women differ from traditional breast cancer risk factors and from factors associated with breast density in pre-menopausal and younger post-menopausal women.

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PubMed2005

The determinants of plasma plasminogen activator inhibitor-1 levels differ for American and Japanese men aged 40-49.

BACKGROUND: Elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels were associated with higher incidence of type II diabetes. Elucidating the determinants of PAI-1 in various ethnicities may help to understand the susceptibility to developing diabetes. The aim of our study was to compare PAI-1 levels between Americans and the Japanese in the post-war generation and to elucidate the determinants of the PAI-1 levels. METHODS: We conducted a cross-sectional study on a total of 198 men aged 40-49 in the US (Body mass index (BMI): 27.0+/-3.3 kg/m(2)) and Japan (BMI: 23.3+/-3.1 kg/m(2)). Examination included physique measurement (BMI and waist girth), blood analysis (lipid profiles, glucose, insulin, C-reactive protein, and PAI-1), and life-style assessment by self-administered questionnaires. RESULTS: PAI-1 levels were significantly lower in American than in Japanese men, even after adjustment for age, waist girth, cigarette smoking, habitual alcohol drinking, and other factors. In the Americans, waist girth, insulin, and cigarette smoking were significantly associated with PAI-1 levels, while waist girth and triglycerides were significantly associated with PAI-1 levels in the Japanese. CONCLUSIONS: PAI-1 levels were significantly lower in American than in Japanese men and the determinants of PAI-1 levels differ for American and Japanese men aged 40-49.

Adult↗
PubMed2005

Relationship between premenopausal dietary intake and postmenopausal subclinical atherosclerosis.

OBJECTIVES: This study examines the association of premenopausal dietary intake with postmenopausal subclinical atherosclerosis. DESIGN: A prospective population-based cohort of 401 premenopausal women from the Healthy Women Study. Baseline premenopausal dietary intake was determined with the use of single 24-h recall. Coronary and aortic calcium scores were measured by electron beam computed tomography 8 years after menopause, and carotid plaque index was measured by carotid ultrasound scan 5 years after menopause. RESULTS: Prevalence of coronary, aortic, and carotid subclinical atherosclerosis were 47.3%, 75.4%, and 52.1%, respectively. In unadjusted analysis, the relative risks (RR) of saturated fat intake for coronary calcification in second, third and highest quartile groups compared to the lowest were 1.82 (95% confidence interval, 1.00-3.30), 1.49 (0.82-2.70), and 1.99 (1.09-3.62), while those of carbohydrate intake were 0.48 (95% confidence interval, 0.26-0.88), 0.47 (0.26-0.86), and 0.35 (0.19-0.64), respectively. None of the dietary components were significantly associated with aortic calcification or carotid plaque. CONCLUSION: The association between premenopausal dietary intake and postmenopausal subclinical atherosclerosis supports the recommended premenopausal dietary intervention for the prevention of cardiovascular disease.

Adult↗
PubMed2005

Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study.

BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype. METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly. RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI, 0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03 (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors. CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.

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PubMed2005

C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study.

BACKGROUND: High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available. METHODS AND RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age without prior vascular diseases; 26% had elevated concentrations (>3 mg/L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33% in men and 17% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with <1 mg/L was 1.82 (95% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 (95% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10% to 20%, the observed CHD incidence was 32% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk >20%; the incidences were 31% and 10% for elevated and normal CRP levels, respectively. CONCLUSIONS: In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women.

Age Factors↗
PubMed2005

Suicides following bariatric surgery for the treatment of obesity.

The proportion of the United States population living with bariatric surgery has increased exponentially since the mid 1990s. It is pertinent to study and understand the mortality patterns of this emergent population cohort and determine the role bariatric surgery may play in these mortality patterns. We present the forensic and clinical characteristics of three cases of suicide following bariatric surgery for the treatment of morbid obesity. The clinical history in each case included recurrent major depressive disorder before and after surgery. Surgery-suicide intervals were 12 months, 27 months and 26 months, respectively. Pre-surgery and pre-mortem body mass indices were 37.7 and 22.2 kg/m(2); 42.0 and 25.0 kg/m(2); 39.5 and 29.4 kg/m(2). Depressive disorder may persist in the bariatric surgery patient despite successful surgical control of obesity.

Adult↗
PubMed2005

Marital quality and occurrence of the metabolic syndrome in women.

BACKGROUND: Marital status is associated with the early stages and progression of cardiovascular disease, an association that may stem in part from the influence of marital quality on metabolic factors. The objective of this study was to examine whether women reporting marital satisfaction are at reduced risk of developing the metabolic syndrome compared with other women. METHODS: Four hundred thirteen middle-aged women from the Pittsburgh Healthy Women Study completed measures of marital status and marital satisfaction at baseline and 3 years later. Metabolic syndrome (diagnosed according to the criteria of the National Cholesterol Education Program) was assessed at baseline and at the last follow-up visit (an average of 11.5 years later). RESULTS: Compared with maritally satisfied women, maritally dissatisfied (odds ratio [OR], 3.02; 95% confidence interval [CI], 1.46-6.24), divorced (OR, 2.47; 95% CI, 1.02-5.97), and widowed (OR, 5.82; 95% CI, 1.88-18.03) women were significantly more likely to have the metabolic syndrome at follow-up. The differences between maritally satisfied women and dissatisfied (OR, 3.18; 95% CI, 1.42-7.15) and widowed (OR, 5.69; 95% CI, 1.70-9.04) women remained significant in the full multivariate model. The difference between maritally satisfied women and divorced women (OR, 2.35; 95% CI, 0.89-6.18) was reduced to marginal significance in the full multivariate model. Single (OR, 2.84; 95% CI, 0.84-9.64) and moderately satisfied (OR, 1.06; 95% CI, 0.35-3.21) women did not differ significantly from maritally satisfied women. CONCLUSIONS: Women in high-quality marriages are at lower risk of developing the metabolic syndrome. Social histories of patients should include assessment of marital quality.

Adult↗
PubMed2005

Event-related functional magnetic resonance imaging investigation of executive control in very old individuals with mild cognitive impairment.

BACKGROUND: Attentional control of executive cognitive function (ECF) decreases in older individuals with Alzheimer Disease (AD). In order to examine early AD-related changes in the neural substrates of ECF attentional control, we measured activation dorsolateral prefrontal (dLPFC), posterior parietal (PPC), and anterior cingulate cortex (ACC) in adults with mild cognitively impairment (MCI) and in cognitively normal (CN) adults. METHODS: Functional magnetic resonance imaging analysis of brain activation in MCI (n = 8, mean age 79.5) and CN (n = 8 mean age 81.5) during increasing loads of attentional demands. RESULTS: MCI and CN older adults performed with similar accuracy and reaction time. MCI had greater activation than CN in PPC (right p = .03 and left p = .05) and dlPFC areas (right p = .002 and left p = .004), while activation in ACC was similar in the two groups. Response to increasing loads of the task differed by group: MCI selectively engaged bilateral PPC (right p = .03, left p = .04), while CN subjects increased bilateral dlPFC activation (right p = .005 and left p = .02) and ACC activation (p = .04). Among MCI, greater load-related changes in PPC activity were associated with smaller load-related changes in accuracy rates (r = -.85, p = .07) and greater increases in reaction times (r = .97, p = .01). In CN subjects, load-related change in PPC activation was associated with load-related change in reaction time (r = .76, p = .02) but not with changes in accuracy rates. CONCLUSIONS: PPC and dlPFC may show early functional changes associated with MCI.

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PubMed2005

Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study.

Physical activity may help preserve cognitive function and decrease dementia risk, but epidemiologic findings are inconsistent. The authors conducted a prospective study to determine the association between physical activity and risk of dementia, Alzheimer's disease, and vascular dementia. The US study population comprised 3,375 men and women aged 65 years or older, free of dementia at baseline, who participated in the Cardiovascular Health Cognition Study in 1992-2000. Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated. Analyses were based on Cox proportional hazards models. There were 480 incident cases of dementia over an average of 5.4 years of follow-up. After multivariate adjustment, participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 (95% confidence interval: 0.61, 1.19) compared with those in the lowest quartile, and participants engaging in >or=4 activities had a relative risk of dementia of 0.51 (95% confidence interval: 0.33, 0.79) compared with those engaging in 0-1 activity. These associations were more marked in apolipoprotein E genotype (APOE) epsilon4 allele noncarriers but were absent in carriers. A similar pattern was observed for Alzheimer's disease and vascular dementia. Mechanisms to explain the observed relations deserve further study.

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PubMed2005

Hormone therapy, lipoprotein subclasses, and coronary calcification: the Healthy Women Study.

BACKGROUND: The Women's Health Initiative (WHI) clinical trial found no reduction in coronary heart disease events among hormone therapy (HT) users despite an improvement in lipid levels. We hypothesized that a lack of benefit of HT on atherosclerosis would be better explained by the lipoprotein subclasses than by standard lipid levels. To test this hypothesis, we evaluated differences in coronary calcification, lipids, and lipoprotein subclasses among HT users and nonusers in a longitudinal study of the menopause. METHODS: Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary artery calcification (CAC) determined by electron beam computed tomography were compared between HT users (49%) and nonusers among 243 women, approximately 8 years postmenopausal, from the Healthy Women Study. RESULTS: The distribution of CAC scores was not significantly different between HT users and nonusers. As expected, HT users had higher levels of large high-density lipoprotein (HDL) particles and large very low-density lipoprotein (VLDL) particles. However, despite lower low-density lipoprotein (LDL) cholesterol levels among HT users, there were no significant differences between HT users and nonusers in any LDL subclass measures, including particle size or concentration. Regardless of HT use, women with CAC had higher levels of large VLDL and small LDL particles, higher LDL particle concentration, and smaller mean LDL size compared with women with no detectable CAC. CONCLUSIONS: Compared with nonusers, HT users had higher levels of VLDL particles (triglycerides) and did not have a better LDL subclass distribution, which may explain the failure of HT to be associated with a difference in CAC in our study or with a reduction in coronary heart disease risk in randomized clinical trials.

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PubMed2005

Incidence of type 2 diabetes in the randomized multiple risk factor intervention trial.

BACKGROUND: Weight loss and increased physical exercise reduce the risk for diabetes in people with impaired glucose tolerance. Randomized trial evidence on the effect of these interventions on people without impaired glucose tolerance is lacking. OBJECTIVE: To examine the influence of a comprehensive intervention program on the risk for developing diabetes in men without impaired glucose tolerance and in a post hoc subgroup analysis by baseline cigarette smoking status. DESIGN: Randomized, controlled trial. SETTING: 22 clinical centers for the Multiple Risk Factor Intervention Trial (MRFIT). PARTICIPANTS: 12,866 men age 35 to 57 years at risk for cardiovascular disease were randomly assigned to either a special intervention or usual care group and followed for 6 to 7 years; this report focuses on 11,827 men without diabetes or impaired glucose tolerance at entry for whom follow-up glucose measurements were available. MEASUREMENTS: Cardiovascular disease risk factors, fasting blood glucose levels, and diabetes medication history were assessed before randomization and annually. INTERVENTION: Men in the special intervention group were counseled to change diet (reduce saturated fat, cholesterol, and calorie intake), to stop smoking, and to increase physical activity. Blood pressure was treated more intensively in the special intervention group than in the usual care group. RESULTS: 11.5% of the special intervention group and 10.8% of the usual care group developed diabetes over 6 years of follow-up (hazard ratio, 1.08 [95% CI, 0.96 to 1.20]). The special intervention-usual care hazard ratio for diabetes was 1.26 (CI, 1.10 to 1.45) among smokers (63%) and 0.82 (CI, 0.68 to 0.98) among nonsmokers (37%). These estimates differed significantly (P = 0.0003). Weight gain after smoking cessation and the use of antihypertensive drugs may have counterbalanced the beneficial effect of the lifestyle intervention for the special intervention group smokers, while the lifestyle intervention was beneficial among nonsmokers. LIMITATIONS: Principal findings are based on a post hoc subgroup analysis. CONCLUSIONS: In nonsmokers, an intervention program that included nutrition counseling to produce reductions in weight, serum cholesterol, and (along with antihypertensive medication) blood pressure reduced the risk for diabetes.

Adult↗
PubMed2005

Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.

Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.

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