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Biomedical subjects

L H Kuller

Publications and source records attributed to L H Kuller.

At least 73 records · Page 4Linked to original sources
PubMed2000

Diabetes mellitus: subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality.

Previously diagnosed diabetes mellitus, newly diagnosed diabetes mellitus, and impaired glucose tolerance are important determinants of the risk of clinical cardiovascular disease (CVD). We have evaluated the relation of patients with subclinical CVD, diabetes, and impaired glucose tolerance and "normal" subjects and the risk of clinical CVD in the Cardiovascular Health Study. Diabetes (1343), impaired glucose tolerance (1433), and normal (2421) were defined by World Health Organization criteria at baseline in 1989 to 1990. The average follow-up was 6.4 years (mean age 73 years). Diabetics had a higher prevalence of clinical and subclinical CVD at baseline. Compared with diabetes in the absence of subclinical disease, the presence of subclinical CVD and diabetes was associated with significant increased adjusted relative risk of death (1.5, CI 0.93 to 2.41), relative risk of incident coronary heart disease (1.99, CI 1.25 to 3.19), and incident myocardial infarction (1.93, CI 0.96 to 3.91). The risk of clinical events was greater for participants with a history of diabetes compared with newly diagnosed diabetics at baseline. Compared with nondiabetic nonhypertensive subjects without subclinical disease, patients with a combination of diabetes, hypertension, and subclinical disease had a 12-fold increased risk of stroke. Fasting blood glucose levels were a weak predictor of incident coronary heart disease as were most other risk factors. Subclinical CVD was the primary determinant of clinical CVD among diabetics in the Cardiovascular Health Study.

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PubMed2000

Vascular imaging: changing the face of cardiovascular research.

Patients with systemic lupus erythematosus (SLE) are at significant risk for premature cardiovascular disease, now a leading cause of death in this population. Most previous studies have used an overt clinical event to identify cardiovascular disease, likely underestimating the actual prevalence in these patients. Although the rates of myocardial infarction in SLE are high, the actual number of coronary events is low, precluding large clinical trials using a coronary event as the sole outcome. The ability to measure atherosclerosis, a known determinant of coronary heart disease, provides investigators with a desirable surrogate for the clinical cardiac event. With the advent of sensitive imaging techniques to identify subclinical atherosclerosis, we are now better equipped to determine the true prevalence and mechanisms of vascular disease in SLE. In this review, we will discuss several vascular imaging techniques and the current trend away from measuring flow-limiting vessel stenosis toward measuring earlier structural and functional aspects of the vascular system.

Arteriosclerosis↗
PubMed2000

Apolipoprotein E gene polymorphism and bone loss: estrogen status modifies the influence of apolipoprotein E on bone loss.

The identification of genes that contribute to bone mineral density (BMD) and bone loss has widespread implications for the understanding and prevention of osteoporosis. The objective of this study was to examine the relationship between the presence and absence of the apolipoprotein E*4 (APOE*4) allele and both BMD and annualized percentage rate of change in BMD at the lumbar spine and hip in a population of 392 healthy, pre-, peri-, and postmenopausal white women participating in the Women's Healthy Lifestyle Project. APOE genotype was analyzed by restriction enzyme analysis from genomic DNA. BMD at the lumbar spine and hip was measured at baseline and after a mean of 2.5 years using dual-energy X-ray absorptiometry (DXA). In premenopausal women, there were no significant differences in BMD or in the annualized percentage rate of change in BMD at the spine or hip when comparing women with and without the APOE*4 allele. In contrast, spine bone loss was significantly greater in peri- and postmenopausal women having an APOE*4 allele than in women without this allele (-1.75 + 1.5% per year vs. -0.98 +/- 1.4% per year, respectively, p = 0.018). Among peri- and postmenopausal women currently using hormone replacement therapy (HRT), there were no differences in the annualized percentage rate of change in spine BMD; whereas, among non-HRT users, there was a 2-fold higher rate of spine bone loss in women with an APOE*4 allele compared with women without this allele (-2.31 +/- 1.5% per year vs. -1.27 +/- 1.3% per year, respectively, p = 0.033; APOE*4 x HRT interaction, p = 0.076). In conclusion, this study shows the importance of APOE*4 allele in spine bone loss in peri- and postmenopausal women and, more importantly, it provides evidence for a genetic and lifestyle interaction in modulating spine bone loss.

Adult↗
PubMed2000

Race and gender differences in the effects of smoking on lung function.

STUDY OBJECTIVE: To assess the extent to which the relationship between smoking and lung function in adults varies by gender and race/ethnicity. DESIGN: A random-effects metaregression analysis to synthesize results from common cross-sectional regression models fit to participants in each of 10 gender-race strata in each of eight large population-based observational studies or clinical trials. SETTING: Source data collected as part of the most recently completed examination cycle for each of the participating studies. PARTICIPANTS: Participants ranged in age from 30 to 85 years, although the age, race, gender, and general health characteristics of each of the populations varied greatly. INTERVENTIONS: Most of the studies were observational in nature, although some did involve lifestyle interventions. All treatment assignments were ignored in the analysis. MEASUREMENTS AND RESULTS: All studies measured lung function using standardized methods with centrally trained and certified technicians. Study findings confirm statistically significant, dose-related smoking effects in all race-gender groups studied. Significant gender differences in the effects of cigarette smoking were seen only for blacks; black men who smoked had greater smoking-related declines in FEV(1) than did black women. This effect was present in only one of two smoking models, however. Significant racial differences in the effects of smoking were seen only for men, with Asian/Pacific Islanders having smaller smoking-related declines than white men in both models. CONCLUSIONS: In summary, this analysis generally failed to support the hypothesis of widespread differences in the effects of cigarette smoking on lung function between gender or racial subgroups.

Adult↗
PubMed2000

Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes.

In light of an occurring growth of elderly people affected by type 2 diabetes and recent observations indicating that type 2 diabetes may be a disease of the innate immune system, we evaluated whether signs of islet cell autoimmunity are associated with an abnormal glucose control, the presence of insulin requirement, or an activation of the acute-phase response in older individuals with type 2 diabetes. GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. No differences were seen in the percentage of insulin requirement in the two groups. Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. In conclusion, in type 2 diabetic subjects > or =65 years old, the presence of islet cell autoimmunity is associated with an impairment of the acute-phase insulin secretion, as revealed by an OGTT. A pronounced activation of the acute-phase response, found to be associated with islet cell autoimmunity, may in part explain this defect in insulin secretion. These findings not only have direct implications for adequate classification and treatment of diabetes in the elderly, but also for understanding the autoimmune/inflammatory mechanisms involved in the pathogenesis of hyperglycemia.

Aged↗
PubMed2000

Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical coronary artery disease in men than in women.

We studied the relationship of coronary artery calcification (CAC), a marker of coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD) and established cardiovascular disease (CVD) risk factors in a type 1 diabetic population. At the 10-year follow-up examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8 years) received electron beam tomography (EBT) scanning of the heart and a clinical examination. Clinical CAD was defined as a confirmed history of myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A CACS cut point of 400 was the most efficient coronary calcium correlate of CAD. In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and Beck Depression Inventory independently correlated with prevalent CAD in men and overall. Except for CAC, the same variables independently correlated with CAD in women, and age also entered the model. CAC was an independent correlate of MI or obstructive CAD in both sexes and was the strongest independent correlate in men, but CAC was not independently associated with angina and ischemic ECG in either sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in type 1 diabetes-particularly in men.

Adult↗
PubMed1999

Circular epidemiology.

Circular epidemiology can be defined as the continuation of specific types of epidemiologic studies beyond the point of reasonable doubt of the true existence of an important association or the absence of such an association. Circular epidemiology is an extreme example of studies of the consistency of associations. A basic problem for epidemiology is the lack of a systematic approach to acquiring new knowledge to reach a goal of improving public health and preventive medicine. For epidemiologists, research support unfortunately is biased toward the continued study of already proven hypotheses. Circular epidemiology, however, freezes at one point in the evolution of epidemiologic studies, failing to move from descriptive to analytical case-control and longitudinal studies, for example, to experimental, clinical trials. Good epidemiology journals are filled with very well-conducted epidemiologic studies that primarily repeat the obvious or are variations on the theme.

Bias↗
PubMed1999

Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria.

BACKGROUND: The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly. METHODS: We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria. FINDINGS: There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%). INTERPRETATION: The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.

Age Factors↗
PubMed1999

Increased blood glucose and insulin, body size, and incident colorectal cancer.

BACKGROUND: Abdominal obesity--an elevated level of visceral adipose tissue--has been linked to colorectal cancer. Furthermore, elevated levels of visceral adipose tissue have been associated with hyperinsulinemia, and insulin is a growth factor in the colon. We assessed whether waist circumference, a surrogate measure of visceral adipose tissue, and metabolic parameters associated with visceral adipose tissue were related to colorectal cancer. METHODS: In the Cardiovascular Health Study cohort, we examined the relationship of baseline measurements of body size, glucose, insulin, and lipoproteins to incident colorectal cancer. All P values are two-sided. RESULTS: Among 5849 participants, 102 incident cases of colorectal cancer were identified. Individuals in the highest quartile of fasting glucose had a nearly twofold increased risk of colorectal cancer (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.0-3.1), and the linear trend RR (LT RR = 1.2; 95% CI = 1.0-1.5) for fasting glucose level was statistically significant (P =. 02). Glucose and insulin levels 2 hours after oral glucose challenge also exhibited statistically significant associations with colorectal cancer (2-hour glucose levels: RR = 2.4 [95% CI = 1.2-4. 7]/LT RR = 1.3 [95% CI = 1.0-1.6; P =.02]; 2-hour insulin levels: RR = 2.0 [95% CI = 1.0-3.8]/LT RR = 1.2 [95% CI = 1.0-1.5; P =.04]). Analysis of fasting insulin levels suggested a threshold effect, with values above the median associated with colorectal cancer (RR = 1.6; 95% CI = 1.1-2.4; P =.02). Higher levels of waist circumference were also statistically significantly associated with colorectal cancer (RR = 1.9; 95% CI = 1.1-3.3; P =.02). CONCLUSIONS: These data provide, to our knowledge, the first direct evidence of an association between elevated visceral adipose tissue level, its associated metabolic effects, and colorectal cancer.

Adipose Tissue↗
PubMed1999

Electrocardiographic left ventricular hypertrophy by five criteria among civil servants in Benin City, Nigeria: prevalence and correlates.

Although increasing hypertension rates have been reported in several African populations, little is known about the frequency of resulting hypertensive complications in these populations. We recorded the electrocardiograms of 482 male and 284 female civil servants in Benin City, Nigeria. Five different criteria were used to detect the presence of electrocardiographic left ventricular hypertrophy. Associations between electrocardiographic left ventricular hypertrophy and demographic, anthropometric and blood pressure characteristics were assessed. The prevalence of electrocardiographic left ventricular hypertrophy ranged from 3 to 29% in the total population, depending on the criteria used, with four of the five criteria resulting in prevalence estimates of less than 10%. The prevalence of electrocardiographic left ventricular hypertrophy was significantly greater among those with hypertension (19% of the total population), ranging from 11 to 49%. The prevalence of electrocardiographic left ventricular hypertrophy increased with blood pressure level in both normotensives and hypertensives. Among hypertensives with systolic blood pressure > or =180 mm Hg or diastolic blood pressure > or =110 mm Hg, the prevalence exceeded 50% by four of the five criteria. We conclude that left ventricular hypertrophy may be affecting many hypertensives in this Nigerian population, potentially resulting in a substantial future burden of cardiovascular disease and death.

Adult↗
PubMed1999

Traditional risk factors and subclinical disease measures as predictors of first myocardial infarction in older adults: the Cardiovascular Health Study.

BACKGROUND: Risk factors for myocardial infarction (MI) have not been well characterized in older adults, and in estimating risk, we sought to assess the individual and joint contributions made by both traditional risk factors and measures of subclinical disease. METHODS: In the Cardiovascular Health Study, we recruited 5888 adults aged 65 years and older from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination that included traditional risk factors such as blood pressure and fasting glucose level and measures of subclinical disease as assessed by electrocardiography, carotid ultrasonography, echocardiography, pulmonary function, and ankle-arm index. Participants were followed up with semiannual contacts, and all cardiovascular events were classified by the Morbidity and Mortality Committee. The main analytic technique was the Cox proportional hazards model. RESULTS: At baseline, 1967 men and 2979 women had no history of an MI. After follow-up for an average of 4.8 years, there were 302 coronary events, which included 263 patients with MI and 39 with definite fatal coronary disease. The incidence was higher in men (20.7 per 1000 person-years) than women (7.9 per 1000 person-years). In all subjects, the incidence was strongly associated with age, increasing from 7.8 per 1000 person-years in subjects aged 65 to 69 years to 25.6 per 1000 person-years in subjects aged 85 years and older. Glucose level and systolic blood pressure were associated with the incidence of MI, but smoking and lipid measures were not. After adjustment for age and sex, the significant subclinical disease predictors of MI were borderline or abnormal ejection fraction by echocardiography, high levels of intimal-medial thickness of the internal carotid artery, and a low ankle-arm index. Forced vital capacity and electrocardiographic left ventricular mass did not enter the stepwise model. Excluding subjects with clinical cardiovascular diseases such as prior angina or congestive heart failure at baseline had little effect on these results. Risk factors were generally similar in men and women. CONCLUSIONS: After follow-up of 4.8 years, systolic blood pressure, fasting glucose level, and selected subclinical disease measures were important predictors of the incidence of MI in older adults. Uncontrolled high blood pressure may explain about one quarter of the coronary events in this population.

Age Distribution↗
PubMed1999

Prevalence and risk factors for abdominal aortic aneurysms in older adults with and without isolated systolic hypertension.

An association between abdominal aortic aneurysm (AAA) and atherosclerotic disease has been recognized and may be due to shared risk factors. A consistent relation between blood pressure and AAA has not been found. AAA was compared between those with and without isolated systolic hypertension (ISH) and prevalence of aortic atherosclerosis was evaluated. Abdominal aortic ultrasound was performed in 266 people, 143 with ISH and 123 age-similar controls. AAA was defined as an infrarenal aortic diameter of > or = 3.0 cm or an infrarenal-to-suprarenal diameter ratio of > or = 1.2. The average age of participants was 73 years. Overall prevalence of AAA was 9.4%, 11.9% in those with ISH and 6.5% among normotensives (p = 0.134). Multivariate analysis revealed male gender (p <0.001), higher low-density lipoprotein (p <0.001), higher pulse pressure (p = 0.032), and current smoking (p = 0.012) to be independent predictors of AAA. When evaluating aortic atherosclerosis, those with AAA had significantly larger diameters of the iliac arteries along with greater intimamedia thickness of the iliac arteries. Those with and without aneurysms had a similar prevalence of plaque (89% to 96%), but measured plaques tended to be larger among those with than without AAA (p <0.001). Progression of AAA after 1 year was observed in 8 participants, with a mean diameter change of 3.42 mm. AAA was found to be independently associated with pulse pressure but not with systolic blood pressure. Patients with AAA also had greater wall thickness and greater diameter of the iliac arteries, which are probably associated with the underlying disease process.

Age Factors↗
PubMed1999

Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Study of Osteoporotic Fractures Research Group.

BACKGROUND: The relation between endogenous steroid hormones and risk for breast cancer is uncertain. Measurement of sex hormone levels may identify women at high risk for breast cancer who should consider preventive therapies. OBJECTIVE: To test the hypothesis that serum concentrations of estradiol and testosterone predict risk for breast cancer. DESIGN: Prospective case-cohort study. SETTING: Four clinical centers in the United States. PARTICIPANTS: 97 women with confirmed incident breast cancer and 244 randomly selected controls; all women were white, 65 years of age or older, and were not receiving estrogen. MEASUREMENTS: Sex-steroid hormone concentrations were assayed by using serum that was collected at baseline and stored at -190 degrees C. Risk factors for breast cancer were ascertained by questionnaire. Incident cases of breast cancer were confirmed by review of medical records during an average period of 3.2 years. RESULTS: The relative risk for breast cancer in women with the highest concentration of bioavailable estradiol (> or = 6.83 pmol/L or 1.9 pg/mL) was 3.6 (95% CI, 1.3 to 10.0) compared with women with the lowest concentration. The risk for breast cancer in women with the highest concentration of free testosterone compared with those with the lowest concentration was 3.3 (CI, 1.1 to 10.3). The estimated incidence of breast cancer per 1000 person-years was 0.4 (CI, 0.0 to 1.3) in women with the lowest levels of bioavailable estradiol and free testosterone compared with 6.5 (CI, 2.7 to 10.3) in women with the highest concentrations of these hormones. Traditional risk factors for breast cancer were similar in case-patients and controls. Adjustments for these risk factors had little effect on the results. CONCLUSIONS: Estradiol and testosterone levels may play important roles in the development of breast cancer in older women. A single measurement of bioavailable estradiol and free testosterone may be used to estimate a woman's risk for breast cancer. Women identified as being at high risk for breast cancer as determined by these hormone levels may benefit from antiestrogen treatment for primary prevention.

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