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L H Kuller

Publications and source records attributed to L H Kuller.

At least 91 records · Page 5Linked to original sources
PubMed1999

Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology.

An increasing number of cardiovascular epidemiologic studies are measuring non-traditional risk markers of disease, most of which do not have established biovariability characteristics. When biovariability data have been reported, they usually represent a short time period, and, in any case, there is little consensus on how the information should be used. The authors performed a long-term (6-month) repeated measures study on 26 healthy individuals, and, using a nested analysis of variance (ANOVA) approach, report on the analytical (CVA), intraindividual (CVI), and between individual (CVG) variability of 12 procoagulant, fibrinolysis, and inflammation assays, including total cholesterol for comparison. The results suggest acceptable analytical variability (CVA < or = 1/2 CVI) for all assays. However, there was a large range of intraindividual variation as a proportion of total variance (2-78%), and adjusting for intraindividual and between individual variation in bivariate correlations increased the observed correlation by more than 30 percent for three of these assays. Overall, the assays showed a significant increase in intraindividual variation over 6 months (p < 0.05). While these findings suggest that most of these assays have biovariability characteristics similar to cholesterol, there is variation among assays. Some assays may be better suited to epidemiologic studies, and knowledge of an assay's biovariability data may be useful in interpreting simple statistics, and in designing multivariate models.

Adult↗
PubMed1999

Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of carotid atherosclerosis and associated risk factors in women with systemic lupus erythematosus (SLE). METHODS: Carotid plaque and intima-media wall thickness (IMT) were measured by B-mode ultrasound in women with SLE. Risk factors associated with carotid plaque and IMT were determined at the time of the ultrasound scan and included traditional cardiovascular risk factors, SLE-specific variables, and inflammation markers. RESULTS: The 175 women with SLE were predominantly white (87%), with a mean age of 44.9 years (SD 11.5). Twenty-six women (15%) had a previous arterial event (10 coronary [myocardial infarction or angina], 11 cerebrovascular [stroke or transient ischemic attack], and 5 both). The mean +/- SD IMT was 0.71 +/- 0.14 mm, and 70 women (40%) had focal plaque. Variables significantly associated with focal plaque (P < 0.05) included age, duration of lupus, systolic, diastolic, and pulse pressure, body mass index, menopausal status, levels of total and low-density lipoprotein (LDL) cholesterol, fibrinogen and C-reactive protein levels, SLE-related disease damage according to the Systemic Lupus International Collaborating Clinics (SLICC) damage index (modified to exclude cardiovascular parameters), and disease activity as determined by the Systemic Lupus Activity Measure. Women with longer duration of prednisone use and a higher cumulative dose of prednisone as well as those with prior coronary events were more likely to have plaque. In logistic regression models, independent determinants of plaque (P < 0.05) were older age, higher systolic blood pressure, higher levels of LDL cholesterol, prolonged treatment with prednisone, and a previous coronary event. Older age, a previous coronary event, and elevated systolic blood pressure were independently associated with increased severity of plaque (P < 0.01). Older age, elevated pulse pressure, a previous coronary event, and a higher SLICC disease damage score were independently related to increased IMT (P < 0.05). CONCLUSION: B-mode ultrasound provides a useful noninvasive technique to assess atherosclerosis in women with SLE who are at high risk for cardiovascular disease. Potentially modifiable risk factors were found to be associated with the vascular disease detected using this method.

Adrenal Cortex Hormones↗
PubMed1999

Screening mammography and late-stage breast cancer: a population-based study.

BACKGROUND: Among 50- to 69-year-old women, randomized clinical trials show breast cancer mortality reductions from screening mammography. However, few studies examine the long-term health effects and outcomes from screening mammography in community practice. The purpose of this study was to evaluate one approach for determining the effectiveness of screening mammography, as it is practiced in community settings, and to measure the prevalence of prior screening mammography among women with incident breast cancer. METHODS: This study was a population-based survey of the general community. Participants were 406 women with breast cancer diagnosed in 1993. The main outcome measure was breast cancer, late stage at diagnosis or fatal within 2 to 3 years of diagnosis. RESULTS: Sixty-four (57.7%) of 111 women with late-stage and 123 (42.1%) of 292 women with early-stage breast cancer did not have a screening mammogram in the 4 calendar years (1989-1992) before diagnosis. Relative to women with early-stage breast cancer, mammography nonuse in 1989-1992 was significantly more frequent among women with late-stage breast cancer (age-adjusted odds ratio 2.3, 95% confidence interval 1.3-4.3). Prior mammography was particularly infrequent among 42 women with breast cancer incident in 1993 and fatal before January 1996. CONCLUSIONS: Prior mammography among women with late-stage or fatal breast cancer was relatively infrequent. Late-stage or fatal breast cancer lacking prior mammography constitutes a missed public health opportunity. Also, this population-based study showed the expected association between prior mammography and late-stage or fatal breast cancer. These results are consistent with the effective practice of mammography in a community setting. The results illustrate and validate a public health approach that uses prior mammography histories among women with incident breast cancer to evaluate mammography penetration and quality in defined communities.

Aged↗
PubMed1999

Correlates of quantitative ultrasound in the Women's Healthy Lifestyle Project.

Quantitative ultrasound (QUS) assessment of bone is a strong predictor of hip fractures and is currently an FDA-approved tool to identify women at risk of osteoporosis. However, few studies have investigated the lifestyle and genetic correlates of QUS in women. This study investigated the cross-sectional associates of several lifestyle, demographic and genetic factors with calcaneal QUS parameters (broadband ultrasound attenuation (BUA) and speed of sound (SOS)) in 393 women aged 45-53 years. Leisure-time and historical physical activity, dietary calcium and protein, body composition, vitamin D receptor genotypes, menopause status, other health behaviors, calcaneal QUS parameters and bone mineral density (BMD) were assessed at a single clinic visit. Lean mass, recent physical activity and African-American race were the strongest correlates of SOS whereas dietary protein, calcium and recent physical activity were the strongest correlates of BUA. These predictors explained 13% and 6% of the variance in SOS and BUA, respectively. Smoking, alcohol intake, education, hormone replacement therapy, calcium and vitamin D supplements, historical physical activity and vitamin D receptor genotypes were not significantly associated with BUA or SOS. Lean body mass and premenopausal status were the strongest correlates of lumbar BMD whereas lean body mass, physical activity, African-American race and body mass index were significantly related to femoral neck BMD. Physical activity remained predictive of SOS after controlling for lumbar BMD. The spectrum and magnitude of risk factors for SOS and BUA, including lean body mass, physical activity, race, protein and calcium intake, parallel previously observed predictors of BMD.

Black People↗
PubMed1999

Issues of clinical trial design and data interpretations in hypertension.

There are many drug studies for the treatment of hypertension. Most studies compare one drug with another to determine if a drug or class of drugs have unique benefits. In evaluating drug trials, separation of hypertension as compared with atherosclerotic events is important. Trials that focus on prevention of hypertension, especially with new noninvasive markers, may have a bigger part in reducing morbidity and mortality due to elevated blood pressure.

Antihypertensive Agents↗
PubMed1999

Anger, hostility, and visceral adipose tissue in healthy postmenopausal women.

Central obesity is an important risk factor for chronic disease. Its etiology remains unclear. We examined whether anger and hostility, ie, psychological attributes that influence cardiovascular morbidity and mortality, prospectively predict central visceral obesity across 13 years. Visceral adipose tissue (VAT) was determined by x-ray computed tomography (CT) at the L4-L5 disc space in a population-based sample of 157 postmenopausal Healthy Women Study participants. Standardized tests were completed to measure separately trait anger (anger frequency and intensity), style of anger expression (holding anger in and expressing it outwardly), and hostile (mistrustful) attitudes. The higher the VAT score, the higher the trait anger and anger-out scores measured 13 years earlier (Ps < .04) and the higher the concurrent hostile attitudes score (P < .02). Moreover, the higher the VAT score, the greater the increase in trait anger over the study period (P < .03). Trait anger and hostility predicted VAT independent of fasting insulin levels, although both predicted an increase in fasting insulin over time. Women were categorized into three groups according to the distribution of the average percent increase in trait anger and in weight across the study period, respectively. The mean VAT scores increased with the likelihood of being in the highest tertile of increasing trait anger (means: 129.1, 131.1, and 155.8, P < .048) and in the highest tertile of increasing weight (means: 122.4, 131.1, and 162.2, P < .003). The association between a high trait anger score and VAT remained significant, controlling for weight gain. We conclude that hostile attributes, fasting insulin, and weight gain in midlife may contribute to the development of VAT in healthy Caucasian women.

Adipose Tissue↗
PubMed1999

Aging and cardiovascular disease. Use of subclinical measurements.

This article examines the use of subclinical measurements in cardiovascular disease in the elderly. In the past 10 years, the development of new technology to measure subclinical disease has provided the opportunity to evaluate the prevalence of subclinical disease, the risk factors for subclinical disease, and the risk for clinical disease given the presence or absence of subclinical disease.

Aged↗
PubMed1999

Anthropometric and psychosocial determinants of visceral obesity in healthy postmenopausal women.

OBJECTIVE: To identify the best predictor among waist circumference, waist to hip ratio (WHR), weight and body mass index (BMI) of visceral obesity across 8.5-10.8 y. We also examined whether changes in waist across the study period co-occur with changes in psychosocial distress or quality of life, and tested whether action levels of waist (level 1 < 80 cm, level 1-2: 80-87.9 cm, level 2 > or = 88 cm) differentiate between women with varying levels of psychosocial distress and quality of life. SUBJECTS AND MEASUREMENTS: Visceral adipose tissue (VAT) was determined by computerized-tomography at the L4-L5 disc space, and waist circumference, WHR, weight and BMI by anthropometric techniques in a population-based sample of postmenopausal Healthy Women Study participants. Psychosocial distress and quality of life were assessed by standardized tests of personality and behavior. The n varied from 120-345, depending on the research question. RESULTS: Waist circumference was superior over the other anthropometric measures in predicting VAT accounting for 40.1-63.5% of the variance in VAT over the study period (P < 0.001). Associations between symptoms of depression, anxiety or distress, low levels of social support or impaired quality of life with waist circumference were cross-sectional (P < 0.04), with lower levels of distress and less impaired daily functioning being characteristic to women at the action level 1 relative to levels 1-2 or 2. Increasing anger over time was associated longitudinally with increasing waist circumference (P < 0.03). CONCLUSIONS: Identification of healthy women with large waist circumferences is important for prevention and intervention of poor quality of life and chronic disease.

Adipose Tissue↗
PubMed1999

Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial.

BACKGROUND: The positive association between body weight and bone mineral density (BMD) is well documented; in contrast, the effect of changes in body weight on BMD is not well understood, particularly, in normal-weight populations. OBJECTIVE: We examined the effect of a lifestyle intervention aimed at lowering dietary fat intake and increasing physical activity to produce modest weight loss or prevent weight gain on BMD in a population of 236 healthy, premenopausal women aged 44-50 y. DESIGN: All women were participating in a clinical trial known as The Women's Healthy Lifestyle Project and were randomly assigned to intervention or control groups. Dual-energy X-ray absorptiometry of BMD at the lumbar spine and proximal femur were made before and after 18 mo of participation in the trial. RESULTS: The intervention group (n = 115) experienced a mean (+/-SD) weight loss of 3.2 +/- 4.7 kg over the 18 mo compared with a weight gain of 0.42 +/- 3.6 kg in the control group (n = 121) (P < 0.001). The annualized rate of hip BMD loss was 2-fold higher (P < 0.015) in the intervention group (0.81 +/- 1.3%) than in the control group (0.42 +/- 1.1%); a similar, although nonsignificant pattern was observed for the loss in spine BMD: 0.70 +/- 1.4% and 0.37 +/- 1.5% (P = 0.093) in the intervention and control groups, respectively. Large increases in physical activity attenuated spine BMD loss, but had no significant effect on BMD loss at the hip. CONCLUSIONS: The intervention group, who modified their lifestyle to lose weight, had a higher rate of BMD loss at the hip and lumbar spine than did the weight-stable control group. Recommendations for weight loss must be made with consideration that such an endorsement may result in BMD loss.

Adult↗
PubMed1999

Coronary heart disease mortality trends in men in the post World War II birth cohorts aged 35-44 in Japan, South Korea and Taiwan compared with the United States.

BACKGROUND: Since World War II, people in Japan, South Korea, and Taiwan have been exposed to a westernized lifestyle. It is most likely that the post World War II cohorts (1950+) have been more exposed. We hypothesize that there would be an increase in mortality from coronary heart disease (CHD) in men aged 35-44 in these countries. METHODS AND RESULTS: Mortality from CHD in men aged 35-44 in South Korea and Taiwan has recently increased, and in Japan it has decreased. Mortality from CHD in men aged 35-44 is lower in Japan than in either South Korea or Taiwan, and much lower than in the US. National sample data and several epidemiological studies have shown that risk factors for CHD including hypercholesterolaemia and hypertension in the past decade were not much different between young adult men in Japan and the US. Based upon these risk factors, CHD death rates among post World War II cohorts should be similar in Japan and the US. However, the rates are five times higher in the US for men aged 35-44. The majority of deaths in the category of diseases of the heart were from heart failure in men in this age group in Japan; the mortality from heart failure was about three times higher than the mortality from CHD. Heart failure was rarely used in men aged 35-44 in the US. CONCLUSIONS: The continued low mortality rates from CHD in young men in Japan may be an artifact. It is possible that CHD death rates in post World War II birth cohort in Japan are similar to US rates.

Adult↗
PubMed1999

Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.

Coagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (>/=120 microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group.

Age Factors↗
PubMed1999

Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women.

Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, </=0.001). PAP was negatively related to factors associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=-0.26; body mass index, r=-0.26), possibly reflecting an association with plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have sufficient power to detect a significant interaction, PAP and AAI appeared to be more weakly associated in subjects with more manifestations of the IRS: PAP appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic disorders (P</=0.001; slope estimate, -0.14) compared with the subgroup with 2 or more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non-insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP reflects reactive fibrinolysis and is associated with subclinical atherosclerosis, this relationship may be weaker in populations with characteristics of the IRS, possibly reflecting the inhibitory effects of plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence of subclinical disease in subjects with hyperinsulinemia or glucose intolerance is consistent with the premise that depressed plasmin generation may enhance the progression of atherosclerosis in these people.

Aged↗
PubMed1999

Hormone replacement therapy, inflammation, and hemostasis in elderly women.

Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.

Aged↗
PubMed1999

Coronary and aortic calcification among women 8 years after menopause and their premenopausal risk factors : the healthy women study.

In the Healthy Women Study, the relationship between cardiovascular risk factors measured premenopausally at age 48, use of hormone therapy, and coronary and aortic calcification at age 58 were evaluated among 169 women. Approximately 63% of women had no coronary calcification, but only 29% had no aortic calcification. Coronary calcification and aortic calcification were positively correlated with each other. There was a very strong association between low density lipoprotein cholesterol (LDL-C) level and coronary calcification. Among women with premenopausal levels of LDL-C <100 mg/dL, only 9% had a coronary calcium score >/=101 compared with 30% of women with an LDL-C >160 mg/dL. Only 5% of women with a high density lipoprotein cholesterol (HDL-C) level >60 mg/dL had high coronary scores. The level of HDL(2)-C was especially strongly inversely related to coronary calcium scores. Cigarette smoking was a very important determinant of both high aortic and high coronary calcium scores. Other risk factors associated with greater coronary calcium were higher systolic blood pressure, triglycerides levels, and blood glucose. Use of hormone replacement therapy was associated with less coronary calcium (NS). For both hormone replacement therapy users and nonusers, the levels of LDL-C and HDL-C measured premenopausally were predictors of coronary and aortic calcium scores. Thus, risk factors evaluated premenopausally are powerful predictors of coronary and aortic calcification, a marker of atherosclerosis, measured 8 years after menopause, 11 years later in these women.

Aortic Diseases↗
PubMed1999

Genetic variation in apolipoprotein H (beta2-glycoprotein I) affects the occurrence of antiphospholipid antibodies and apolipoprotein H concentrations in systemic lupus erythematosus.

Apolipoprotein H (apoH, protein; APOH, gene) is a required cofactor for the production of antiphospholipid antibodies (APA). In this study we have examined whether genetic variation in the APOH gene affects variation in risk for systemic lupus erythematosus (SLE), occurrence of antiphospholipid antibodies (APA), anti-apoH, and plasma apoH concentrations. A total of 222 white SLE women were screened for four APOH polymorphisms (codons 88, 247, 306, and 316) by polymerase chain reaction, and for plasma apoH concentrations by ELISA. Of these, 29.3% were positive for APA (APA-positive group) and 31.1% for anti-apoH. None of the four APOH polymorphisms were significantly associated with variation in risk for SLE. The codons 306 and 316 polymorphisms showed significant, gene-dosage effects on plasma apoH concentrations (P<0.0001) and explained 30% and 13%, respectively, of the residual variation in apoH concentrations. No significant association was observed between anti-apoH status and APOH polymorphisms or plasma apoH levels. However, plasma apoH concentrations were significantly higher in patients positive for APA than in patients negative for APA (18.5+/-4.0 mg/dl vs 17.1+/-3. 8 mg/dl; P=0.02). The distribution of the Trp316Ser polymorphism was significantly different between the APA-positive and APA-negative groups. The frequency of the mutant allele (Ser316) was significantly lower in the APA-positive group than the APA-negative group (3.1% vs 12.1% P<0.04), indicating that the Ser316 mutation is protective against the production of phospholipid-apoH dependent APA. Our data indicate that common genetic variation in the APOH gene is a significant determinant of plasma apoH variation in SLE patients, and the Trp316Ser polymorphism appears to provide protection against the production of APA in SLE patients.

Adult↗