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L H Kuller

Publications and source records attributed to L H Kuller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sudden cardiac death, genes, and arrhythmogenesis: consideration of new population and mechanistic approaches from a National Heart, Lung, and Blood Institute workshop, Part II.

This is Part II of a 2-part article dealing with malignant ventricular arrhythmias, which are the leading mechanism of death in common cardiac diseases. Genetic population studies directed at discovering common proximal sources of inherited molecular risk most directly linked to arrhythmia initiation and propagation would appear to have considerable potential in helping reduce cardiovascular mortality.

Arrhythmias, Cardiac↗
PubMed2001

Sudden cardiac death, genes, and arrhythmogenesis : consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, part I.

Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation, in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality.

Arrhythmias, Cardiac↗
PubMed2001

Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.

BACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure. METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified. RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension. CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.

Aged↗
PubMed2001

Usefulness of electron beam tomography to detect progression of coronary and aortic calcium in middle-aged women.

Electron beam tomography (EBT) permits the noninvasive quantification of coronary and aortic calcium as a marker of atherosclerosis. Coronary and aortic calcium are strongly related to premenopausal cardiovascular risk factors in middle-aged women. This report evaluates changes in coronary and aortic calcium over an average of 18 months in 80 women. Measurement variation over time and between readings is also evaluated in these women who were followed through the menopausal transition. Eight years after menopause, 80 women (average age 63 years) underwent serial EBT of the coronary arteries and aorta separated by 18 months. Calcium scores were based on the number and density of calcific deposits. Duplicate readings were obtained to evaluate the effect of reading variation on calcium scores. At baseline, the median calcium score was 0 in the coronary arteries and 58 in the aorta. Average change in coronary (+11) and aortic (+112) calcium were significantly different from zero (p < 0.001). Reading variability did not contribute significantly to the variation in calcium scores. Extent of calcium in the coronary arteries was associated with progression of calcium in the aorta (p = 0.013). Both coronary and aortic calcium were significantly associated with premenopausal cardiovascular risk factors. Thus, progression of coronary and aortic calcium using EBT can be observed over a short time in healthy middle- aged women.

Adult↗
PubMed2001

Women's Healthy Lifestyle Project: A randomized clinical trial: results at 54 months.

BACKGROUND: The Women's Healthy Lifestyle Project Clinical Trial tested the hypothesis that reducing saturated fat and cholesterol consumption and preventing weight gain by decreased caloric and fat intake and increased physical activity would prevent the rise in LDL cholesterol and weight gain in women during perimenopause to postmenopause. METHODS AND RESULTS: There were 275 premenopausal women randomized into the assessment only group and 260 women into the intervention group. The mean age of participants at baseline was 47 years, and 92% of the women were white. The mean LDL cholesterol was 115 mg/dL at baseline, and mean body mass index was 25 kg/m(2). The follow-up through 54 months was excellent. By 54 months, 35% of the women had become postmenopausal. At the 54-month examination, there was a 3.5-mg/dL increase in LDL cholesterol in the intervention group and an 8.9-mg/dL increase in the assessment-only group (P:=0.009). Weight decreased 0.2 lb in the intervention and increased 5.2 lb in the assessment-only group (P:=0.000). Triglycerides and glucose also increased significantly more in the assessment-only group than in the intervention group. Waist circumference decreased 2.9 cm in the intervention compared with 0.5 cm in the assessment-only group (P:=0.000). CONCLUSIONS: The trial was successful in reducing the rise in LDL cholesterol during perimenopause to postmenopause but could not completely eliminate the rise in LDL cholesterol. The trial was also successful in preventing the increase in weight from premenopause to perimenopause to postmenopause. The difference in LDL cholesterol between the assessment and intervention groups was most pronounced among postmenopausal women and occurred among hormone users and nonusers.

Blood Pressure↗
PubMed2001

Hormone replacement therapy use and menopausal symptoms among women participating in a behavioral lifestyle intervention.

BACKGROUND: The decision to take hormone replacement therapy (HRT) is a choice many women encounter when entering menopause. The purpose of this study was to examine the choice to take HRT while participating in a lifestyle intervention to reduce cardiovascular risk through the menopause. METHODS: The Women's Healthy Lifestyle Project is a randomized clinical trial designed to examine whether a behavioral lifestyle intervention can decrease the expected rise in cardiovascular risk through the menopause. Participants (N = 535) completed questionnaires and were interviewed regarding menopausal symptoms, menopausal status, hot flashes, and HRT use at baseline and 54 months. RESULTS: The intervention was successful in preventing risk elevation through the 54-month visit. At the final visit, there was no difference between the intervention and control groups in the percentage who had become postmenopausal (32.9% vs 35.0%, respectively), there was no difference between control and intervention with HRT use, with 31.2% reporting use of HRT, and there was no difference between groups with menopausal symptoms. The women started HRT an average of 6 months after they missed a period. Baseline risk factors did not predict HRT use at the 54-month visit. CONCLUSIONS: A sizable number of women reported HRT use. The decision to use HRT was not influenced by the lifestyle intervention or their baseline cardiovascular risk, and these women started HRT very early in the peri- to postmenopause. Further, weight loss in the perimenopause did not affect menopausal symptoms.

Adult↗
PubMed2001

Prospective association of lipoprotein(a) concentrations and apo(a) size with coronary heart disease among men in the Multiple Risk Factor Intervention Trial.

In this nested case-control study, lipoprotein (a) [Lp(a)] concentrations and apo(a) isoform size were measured in serum samples obtained from men participating in the prospective Multiple Risk Factor Intervention Trial (MRFIT). Serum from men aged 35 to 57 years and stored for up to 20 years were analyzed for Lp(a) levels (n=736) and isoform size (n=487), respectively. Cases involved nonfatal myocardial infarctions (MI; n=98), documented during the active phase of the study that ended on February 28, 1982 and coronary heart disease (CHD) deaths (n=148) monitored through 1990. Median Lp(a) levels did not differ between cases and controls and mean apo(a) size did not vary between cases and controls in the entire study population. When adjusted for age and Lp(a) concentration, logistic regression analysis indicated that small apo(a) isoforms were associated with CHD deaths among smokers (OR 3.31; 95% CI 1.07-10.28).

Adult↗
PubMed2001

The role of comorbidity in the assessment of intermittent claudication in older adults.

The prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.

Aged↗
PubMed2001

Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women.

The effects of post-menopausal hormone therapy (HRT) on blood coagulation in elderly women are not well defined. We studied associations of HRT use with levels of natural anticoagulant proteins in a cross-sectional study of 3393 women > or = 65 years of age participating in the Cardiovascular Health Study. Protein C antigen and antithrombin were measured in all users (n = 230 unopposed oestrogen; 60 oestrogen/progestin) and a comparison group of 196 age- and race-matched non-users. Compared with non-users, oestrogen use was associated with higher protein C (4.80 vs. 4.30 microg/ml, P < 0.01). Results were similar for oestrogen/progestin (P > 0.05). In both user groups, antithrombin was lower than in non-users (109% for each vs. 115% in non-users, P < 0.001). Adjustment for factors related to prescription of HRT and to anticoagulant protein levels had little impact on the results. For antithrombin, associations with HRT were larger for thinner Caucasian women and black women. Venous thrombosis from HRT may be mediated partly by alterations in antithrombin, but not protein C concentrations. This study extends previous observations to older women, the group at highest risk of venous thromboembolism. Studies of HRT-induced alterations in anticoagulant function in relation to the occurrence of thrombosis with HRT are required.

Aged↗
PubMed2001

Prevention of cardiovascular disease and the future of cardiovascular disease epidemiology.

BACKGROUND: Coronary heart disease is preventable. The improved interpretation of risk factors, in vivo non-invasive measuring of arteries, brain and heart, and proven efficacy of both non-pharmacological and pharmaceutical therapies provides the model for both cardiovascular prevention programmes and new epidemiological studies. METHODS: Risk factors can be subdivided into those related to the development of atherosclerosis with relatively long incubation periods, and risk factors that moderate the changes in atherosclerotic plaque, thrombosis and fibrinolysis, i.e. those with short incubation periods, or proximate risk factors. RESULTS: The level of ApoB containing lipoproteins, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) are the primary determinants of atherosclerosis. Using non-invasive methods of measuring atherosclerosis, we can evaluate the efficacy of intervention to both prevent the development of atherosclerosis and the progression of disease. The importance of proximate risk factors, especially inflammatory markers, is less estimated than long incubation period factors. It is possible that a combination of measures of subclinical atherosclerosis and proximate risk factors may provide the best estimate of the risk of clinical disease, especially among higher risk older individuals. CONCLUSIONS: The measurement of subclinical disease and new proximate risk factors (i.e. inflammation, fibrinolysis) may be useful for comparing reported differences in rates of clinical disease among populations and monitoring the emerging epidemic of cardiovascular disease in countries that currently have low death rates due to cardiovascular disease.

Biomarkers↗
PubMed2001

Changes in cardiovascular risk factors during the perimenopause and postmenopause and carotid artery atherosclerosis in healthy women.

BACKGROUND AND PURPOSE: The objectives of this study were to describe the changes in cardiovascular risk factors during the perimenopausal and early postmenopausal years and correlate those changes in risk factors with carotid intimal-medial thickness (IMT) and plaque index measured 5 to 8 years after menopause. METHODS: Participants were women (n=372) from Allegheny County, Pennsylvania, enrolled in the Healthy Women Study who had been postmenopausal for at least 5 years. Risk factor changes were measured during the perimenopause, ie, between the premenopausal and first year postmenopausal examinations, and during the early postmenopause, ie, between the first and fifth year postmenopausal examinations. Carotid ultrasound scans measured IMT and plaque at examinations 5 to 8 years after menopause among 314 of the women. RESULTS: Increases in LDL cholesterol and triglycerides and declines in HDL cholesterol were greater during perimenopause than postmenopause, whereas increases in blood pressure and fasting glucose levels were greater during postmenopause. Premenopausal systolic and pulse pressure, LDL and HDL cholesterol, triglycerides, and body mass index predicted IMT and plaque. Only the change in pulse pressure between premenopausal and first year postmenopausal examinations was related to both IMT and plaque. CONCLUSIONS: Absolute risk for cardiovascular disease increases substantially in midlife, with a particularly adverse effect on lipid metabolism at the menopause. Premenopausal levels of risk factors are adequate to identify which women should be targeted for intervention.

Blood Glucose↗
PubMed2001

Coronary heart disease mortality among men aged 35-44 years by prefecture in Japan in 1995-1999 compared with that among white men aged 35-44 by state in the United States in 1995-1998: vital statistics data in recent birth cohort.

The levels of risk factors for coronary heart disease (CHD) in men in the post World War II (WWII) birth cohort are almost similar between Japan and the USA, except for the considerably higher prevalence of cigarette smoking in Japan and the much higher prevalence of obesity in the USA. The present study evaluated the CHD mortality among men in the post WWII birth cohort by prefecture in Japan in 1995-1999 and then compared the data with those for white men in different states in the USA. There was a greater than 2-fold difference in CHD mortality among men aged 35-44 by prefecture in Japan: 5.3/100,000 in Kumamoto vs 12.6/100,000 in Tochigi. CHD mortality among men aged 35-44 in the top 3 prefectures in Japan is about half that of white men in the USA and is similar to that of white men in the lowest 3 states. The much lower CHD mortality in Japan does not appear to be caused by differences in the classification of causes of death and the results suggest that there may be strong and important protective factors that reduce the risk of CHD in Japan.

Adult↗
PubMed2001

A common promotor variant in the cytochrome P450c17alpha (CYP17) gene is associated with bioavailability testosterone levels and bone size in men.

Cytochrome P450c17alpha (CYP17) encodes an enzyme with 17a-hydroxylase and 17,20-lyase activities, which is essential for the normal production of adrenal and gonadal androgens. Because androgens have powerful effects on bone growth and metabolism, we determined whether a single base pair (bp) substitution (T-->C) in the promoter region (-34 bp) of CYP17 is associated with sex hormone levels, stature, and femoral mass and size in 333 white men aged 51-84 years (mean +/- SD; 66+/-7 years). Femoral neck bone mineral content (BMC), cross-sectional area (CSA), and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry (DXA). Genotype frequencies did not deviate from Hardy-Weinberg expectations. Serum bioavailable testosterone levels were 20% or 0.5 SDs higher in men with the C/C compared with the T/T genotype, whereas heterozygous men had intermediate hormone levels (p = 0.019). Men with the C/C genotype also were nearly 3 cm taller and had 0.6 SD greater femoral neck CSA than men with the T/T genotype (p < or = 0.01 for both). The association with CSA persisted after adjusting for age, height, and body weight. In contrast, CYP17 genotype was not associated with femoral neck BMC, areal BMD (g/cm2), or estimated volumetric BMD (g/cm3). These results suggest that allelic variation at the CYP17 locus may contribute to the genetic influence on stature and femoral size in men.

Aged↗
PubMed2001

The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.

Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.

Aged↗
PubMed2001

Menopause in type 1 diabetic women: is it premature?

Women with type 1 diabetes have a delayed menarche and a greater prevalence of menstrual disorders than women without diabetes. However, little is known about the menopause transition among type 1 diabetic women. The Familial Autoimmune and Diabetes (FAD) Study recruited both adult individuals who were identified from the Children's Hospital of Pittsburgh Type 1 Diabetes Registry for the years 1950-1964 and their family members. Unrelated nondiabetic control probands and their relatives were also evaluated. Women with type 1 diabetes (n = 143) compared with nondiabetic sisters (n = 186) or unrelated control subjects (n = 160) were more likely to have an older age at menarche (13.5, 12.5, and 12.6 years, respectively, P < 0.001), more menstrual irregularities before 30 years of age (45.7, 33.3, and 33.1%, respectively, P = 0.04), and a younger age at menopause (41.6, 49.9, and 48.0 years, respectively, P = 0.05). This resulted in a 6-year reduction in the number of reproductive years (30.0, 37.0, and 35.2 years, respectively, P = 0.05) for women with type 1 diabetes. Risk factors univariately associated with earlier menopause included type 1 diabetes (hazard ratio [HR] 1.99, P = 0.04), menstrual irregularities before 30 years of age (HR 1.87, P = 0.04), nulliparity (HR 2.14, P = 0.01), and unilateral oophorectomy (HR 6.51, P < 0.0001). Multivariate analysis confirmed that type 1 diabetes (HR 1.98, P = 0.056), menstrual irregularities by 30 years of age (HR 2.36, P = 0.01), and unilateral oophorectomy (HR 9.76, P < 0.0001) were independent determinants of earlier menopause in our cohort. We hypothesize that an earlier menopause, which resulted in a 17% decrease in reproductive years, is a major unstudied complication of type 1 diabetes.

Adult↗
PubMed2001

Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: Subjects with type 1 diabetes are at high risk for many long-term complications, including early mortality and coronary artery disease (CAD). Few data are available on which to base goal levels for two major risk factors, namely blood pressure and lipid/lipoproteins. The objective of this study was to determine at which levels of LDL and HDL cholesterol, triglycerides, and blood pressure the relative risks of type 1 diabetic complications increase significantly. RESEARCH DESIGN AND METHODS: Observational prospective study of 589 patients with childhood-onset type 1 diabetes (<17 years) aged > or =18 years at baseline; 10-year incidence of mortality, CAD, lower-extremity arterial disease, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy. Relative risks were determined using traditional groupings of blood pressure and lipid/lipoproteins, measured at baseline, using the lowest groupings (<100 mg/dl [2.6 mmol/l] LDL cholesterol, <45 mg/dl [1.1 mmol/l] HDL cholesterol, <100 mg/dl [1.1 mmol/l] triglycerides, <110 mmHg systolic blood pressure, and <80 mmHg diastolic blood pressure) as reference. Adjustments for age, sex, and glycemic control were examined. RESULTS: Driven mainly by strong relationships (RR range 1.8-12.1) with mortality, CAD, and overt nephropathy, suggested goal levels are as follows: LDL cholesterol <100 mg/dl (2.6 mmol/l), HDL cholesterol >45 mg/dl (1.1 mmol/l), triglycerides <150 mg/dl (1.7 mmol/l), systolic blood pressure <120 mmHg, and diastolic blood pressure <80 mmHG: Age, sex, and glycemic control had little influence on these goals. CONCLUSIONS: Although observational in nature, these data strongly support the case for vigorous control of lipid levels and blood pressure in patients with type 1 diabetes.

Adult↗
PubMed2001

Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

Aged↗