Biomedical subjects

Donna Arnett

Publications and source records attributed to Donna Arnett.

16 recordsLinked to original sources

PubMed2006

Longitudinal and age trends of metabolic syndrome and its risk factors: the Family Heart Study.

BACKGROUND: We report longitudinal changes in the metabolic syndrome (MetS) in 2,458 participants from 480 families in the Family Heart Study. Participants were examined between 1994-96 (FHS-T1) and 2002-03 (FHS-T2), about 7.4 years apart. Additionally, the impact of medication on estimates of MetS prevalence, and associations of MetS with prevalent coronary heart disease (CHD) and type 2 diabetes (T2D) were studied. METHODS: Three definitions for MetS prevalence were considered. One represented the original (o) National Cholesterol Education Program (NCEP) MetS criteria. Two others considered the confounding of medications effects, respectively (m) lipid medications constituted a categorical diagnostic criterion for lipids variables, and (c) lipids and blood pressure variables were corrected with average clinical trials medications effects. Logistic regression of MetS on CHD and T2D, as well as the trend analysis of MetS by age, were performed. RESULTS: MetS increased from 17.1% in FHS-T1(o) to 28.8% in FHS-T2(o); from 19.7% in FHS-T1(m) to 42.5% in FHS-T2(m); and from 18.4% in FHS-T1(c) to 33.6% in FHS-T2(c). While we observed adverse changes in all risk factors, the greatest increase was for waist circumference (25%). The percentages of MetS were about 2 to almost 3 times higher in ages 50 years and older than in younger ages. The odds of having prevalent CHD were about 2.5 times higher in the subjects classified with MetS than without. CONCLUSION: MetS percentages increased noticeably longitudinally and cross-sectionally with older age. These conclusions were reached with and without considering medication use, but correcting risk factors for medications use affects the MetS prevalence estimates. As found in other studies, MetS was associated with increased odds for prevalent CHD.

Journal Article↗

PubMed2006

Obtaining informed consent for genetic studies: The multiethnic study of atherosclerosis.

Studies of DNA may yield important information about atherosclerosis. To determine how often study participants' consent to examine DNA is denied and the factors associated with that denial, information was collected on participants in the US Multiethnic Study of Atherosclerosis (MESA) during 2000-2004. Permission was sought for preparation of DNA, transformation of cells into cell lines, evaluation of genes related to heart and other health conditions, and access to DNA by private companies. Of the 5,494 participants at entry, 897 (16.3%) refused consent for some items and 247 (4.5%) completely denied consent. At a second examination 18 months later, 819 (15.0%) partially refused and 229 (4.2%) completely denied consent. Age among men (odds ratio per 10 years = 0.68, 95% confidence interval: 0.54, 0.85; p = 0.004), ethnicity (odds ratio for African American = 2.34, 95% confidence interval: 1.66, 3.32; p < 0.001), and field center (p < 0.001) were associated with complete denial. For those giving partial consent, the most common item refused was access to DNA by private companies (baseline: 99%; second examination: 90%); younger age, male gender, and African-American ethnicity were associated with refusal. The authors concluded that a small percentage of participants in epidemiologic studies refuse consent for DNA studies, and the majority are concerned about sharing their DNA data with industry.

Age Factors↗

PubMed2006

Implications of C-reactive protein or coronary artery calcium score as an adjunct to global risk assessment for primary prevention of CHD.

BACKGROUND: C-reactive protein (CRP) or coronary artery calcium (CAC) score have been suggested to identify a higher risk subset of intermediate-risk individuals, who potentially could be considered for more aggressive therapy. In the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated the proportion of intermediate-risk participants whose risk status might change based on additional testing using CRP and/or CAC score. METHODS: Framingham 10-year CHD risk scores (FRS) were calculated and cross tabulations were used to determine the percent of individuals at intermediate-risk by FRS with a CRP >3mg/L and/or CAC score >100 AU. Similar analyses were performed using the gender-specific 75th percentile for CRP and CAC. RESULTS: Of the 30% of participants (N=1450) classified as intermediate-risk by FRS, 30% had a CRP >3mg/L and 33% had a CAC score >100 AU. Among intermediate-risk women, 49% had a CRP >3mg/L compared to 27% of intermediate-risk men (p<0.0001) while the same percent of intermediate-risk women and men (33%) had a CAC score >100 AU. Eleven percent or less of men or women had both a high CRP and CAC score whether conventional or gender-specific cut points were used. When the percent of intermediate-risk individuals with an elevated CRP and/or CAC score in MESA were applied to NHANES III data, over a million intermediate-risk individuals would move to high risk status if CRP or CAC screening directed treatment strategies were uniformly adopted in the U.S. CONCLUSION: There were differences in the number of intermediate-risk individuals reclassified as high risk depending on the screening test used, the cut points selected, and the demographics of the individuals being screened. These data highlight current limitations of broadly using risk markers such as CRP and CAC score in an intermediate-risk population.

Aged↗

PubMed2006

Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention.

Classifications of heart muscle diseases have proved to be exceedingly complex and in many respects contradictory. Indeed, the precise language used to describe these diseases is profoundly important. A new contemporary and rigorous classification of cardiomyopathies (with definitions) is proposed here. This reference document affords an important framework and measure of clarity to this heterogeneous group of diseases. Of particular note, the present classification scheme recognizes the rapid evolution of molecular genetics in cardiology, as well as the introduction of several recently described diseases, and is unique in that it incorporates ion channelopathies as a primary cardiomyopathy.

American Heart Association↗

PubMed2006

The prognostic value of the mitral diastolic filling velocity ratio for all-cause mortality and cardiovascular morbidity in African Americans: the Atherosclerotic Risks in Communities (ARIC) study.

BACKGROUND: Although recent data suggest that the mitral diastolic early-to-late (E/A) ratio may be prognostic in selected population-based cohorts, its predictive value for morbidity and mortality in African Americans has not yet been well studied. METHODS: The study population consisted of African American participants from the Jackson cohort of the Atherosclerotic Risks in Community Study. Three subgroups of E/A ratios were defined: E/A <0.7, E/A 0.7-1.5, and E/A >1.5, using the middle group as reference. Cox proportional hazard models were used to assess the association between the E/A ratio and both all-cause mortality and incident cardiovascular disease (CVD). The mean follow-up period was 6.8 +/- 1.3 years. RESULTS: Of the 2211 participants in the study population (mean age 62 years, 65.1% women), 8.2% had an E/A ratio <0.7, 84.7% had an E/A 0.7-1.5, and 7.1% had an E/A >1.5. An E/A >1.5 was independently associated with all-cause mortality (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.20-4.03) in the multivariable model. An E/A <0.7 was associated with higher all-cause mortality (HR 1.79, 95% CI 1.17-2.73) and incident CVD (HR 1.91, 95% CI 1.29-2.83) compared with a normal E/A in the age and sex adjusted model but was not independently predictive in the multivariable model (P > .05). CONCLUSIONS: In a population-based cohort of middle-aged African Americans, an E/A >1.5 independently predicts all-cause mortality. An E/A >1.5 and an E/A <0.7 were both associated with incident CVD when adjusted for age and sex alone but were not independently predictive in the multivariable analysis.

Black or African American↗

PubMed2005

Haplotype association analysis of AGT variants with hypertension-related traits: the HyperGEN study.

OBJECTIVE: Function of the renin-angiotensin system is important to human hypertension, but its genetic etiology remains elusive. We set out to examine a hypothesis that multiple genetic variants in the system act together in blood pressure regulation, via intermediate phenotypes such as blood pressure reactivity. METHODS: A sample of 531 hypertensive cases and 417 controls was selected from the HyperGEN study. Hypertension-related traits including blood pressure responses to challenges to math test, handgrip and postural change (mathBP, gripBP, and postBP), and body mass index (BMI) were analyzed for association with 10 single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene. Single-marker and haplotype analyses were performed to examine the effects of both individual and multiple variants. Multiple-trait profiling was used to assess interaction of latent intermediate factors with susceptible haplotypes. RESULTS: In Blacks, two SNPs in exon 5 and 3'UTR showed significant association with gripBP, and two promoter SNPs were strongly associated with postBP. In Whites, only borderline association was found for 2 promoter SNPs with mathBP. Haplotype analyses in Blacks confirmed association with gripBP, and detected significant association of a haplotype to BMI (p=0.029). With the interactions modeled, haplotype associations found in Blacks remain significant, while significant associations to BMI (p=0.009) and gripSBP emerged in Whites. CONCLUSION: Genetic variants in regulatory regions of AGT showed strong association with blood pressure reactivity. Interaction of promoter and genic SNPs in AGT revealed collective action of multiple variants on blood pressure reactivity and BMI both in Blacks and in Whites, possibly following different pathways.

Black or African American↗

PubMed2005

Left ventricular concentric remodeling is associated with decreased global and regional systolic function: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The transition from compensatory concentric remodeling to myocardial failure is not completely understood in humans. To investigate determinants of incipient myocardial dysfunction, we examined the association between concentric remodeling and regional LV function in asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Myocardial tagged MRI was performed. Regional myocardial function expressed as peak systolic midwall circumferential strain (Ecc) was analyzed in 441 consecutive studies by HARP (Harmonic Phase) tool. Peak Ecc was correlated with the extent of concentric remodeling determined by the ratio of left ventricular mass to end-diastolic volume (M/V ratio). In men, a gradual decline in peak global Ecc was seen with increasing M/V ratio (test for trend, P<0.001). Among women, however, Ecc tended to be lower only in the fifth compared with the first quintile of M/V ratio (P=0.1). The association of lower Ecc with increasing M/V ratio was regionally heterogeneous but was particularly prominent in the LAD region in men (test for trend, P<0.001) and in women (test for trend, P=0.02). In the right coronary and left circumflex artery territories, these associations were less marked in both genders. CONCLUSIONS: In this cross-sectional study of asymptomatic individuals, concentric left ventricular remodeling was related to decreased regional systolic function. The reduction in regional function, which was more pronounced in the left anterior descending coronary artery territory, may reflect the local transition from compensatory remodeling to myocardial dysfunction.

Atherosclerosis↗

PubMed2005

Left ventricular mass indexed to height and prevalent MRI cerebrovascular disease in an African American cohort: the Atherosclerotic Risk in Communities study.

BACKGROUND AND PURPOSE: Previous studies have demonstrated that echocardiographic left ventricular mass (LVM) is an independent risk factor for stroke in whites. Despite the greater burden of stroke, the echocardiographic predictors of stroke in African Americans remain poorly understood. METHODS: This investigation is a retrospective analysis of prospectively collected data from the Jackson, Miss (all African American), cohort of the Atherosclerotic Risk in the Communities study. Between 1993 and 1995, 2445 participants received an echocardiogram, and a random subset (n=778) received cerebral MRI evaluating presence of infarcts or white matter disease (WMD; >3 on a scale of 0 to 9). Compared with the entire Jackson cohort, the random subset was older, had a lower body mass index (BMI), and a higher systolic blood pressure (SBP). Logistic regression models examined the relations of LVM indexed by height (LVM/height) to MRI findings adjusted for age, gender, BMI, SBP, hypertensive medications, diabetes, total/high-density lipoprotein cholesterol, smoking status, and history of myocardial infarction. RESULTS: The 667 participants (63% women; 62+/-4 years of age) had a high prevalence of hypertension (68%), obesity (46%), echocardiographic left ventricular hypertrophy (49%), MRI stroke (n=133), and WMD (n=92). Adjusted LVM/height was significantly associated with prevalent MRI stroke (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.7; P=0.02) and WMD (OR, 1.5; 95% CI, 1.1 to 1.9; P=0.006; OR expressed per 1 SD LVM/height, 45 g/m). CONCLUSIONS: In this randomized subset of a population-based cohort of African American adults, LVM/height was related to MRI evidence of prevalent cerebrovascular disease. The current study supports the hypothesis that LVM/height is an important risk factor for stroke in multiple ethnicities.

Black or African American↗

PubMed2004

Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q.

High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol, and high levels of triglycerides (TG) are strong predictors of cardiovascular disease risk. Motivated by previous evidence for pleiotropy between cholesterol and TG levels, we conducted bivariate linkage analysis of LDL cholesterol and TG concentration among participants of the Hypertension Genetic Epidemiolgy Network (HyperGEN), one of four networks in the NHLBI sponsored Family Blood Pressure Program Project. All available hypertensive siblings and their first-degree relatives were recruited. Both phenotypes were similarly adjusted for ethnicity, study center, sex, age, age-by-sex interactions, smoking, alcohol consumption, hormone use, diabetes medication use, and waist circumference. Variance component linkage analysis was performed as implemented in SOLAR, using ethnicity-specific marker allele frequencies derived from founders and multipoint IBDs calculated in MERLIN. A maximum genome-wide empirical LOD score of 3.9 was detected on chromosome 21 at 54cM, between markers D21S2055 and D21S1446. This signal overlaps with suggestive and/or significant linkages for total cholesterol, LDL cholesterol, and apolipoprotein B in three other studies and is suggestive of one or more genes on chromosome 21q jointly regulating LDL cholesterol and TG concentration.

Aged↗

PubMed2004

Imputing gene-treatment interactions when the genotype distribution is unknown using case-only and putative placebo analyses--a new method for the Genetics of Hypertension Associated Treatment (GenHAT) study.

There is a sizeable literature on methods for detecting gene-environment interaction in the framework of case-control studies, particularly with reference to the assumption of independence of genotype and exposure. In the context of a clinical trial, wherein gene-drug interactions with regard to outcomes are examined, these methods may be readily applied, as gene and drug are independent by randomization. In an active-controlled trial (experimental treatment vs standard) that has collected genotype information, gene-drug interactions can be estimated. In addition, the effect of the experimental treatment vs placebo can be imputed by using data from a historical placebo-controlled trial (standard vs placebo) if either (a) genotype information is available from the historical trial or (b) assumptions are made about the prevalence of genotype and the odds ratios of genotype and disease in the historical trial using information from other studies. Motivation for these procedures is provided by the Genetics of Hypertension Associated Treatment, a large pharmacogenetics, ancillary study of a hypertension clinical trial, and examples from published hypertension trials will be used to illustrate the methods.

Controlled Clinical Trials as Topic↗

PubMed2004

Linkage analysis of diabetes status among hypertensive families: the Hypertension Genetic Epidemiology Network study.

Type 2 diabetes susceptibility is determined by multiple genetic and environmental factors. Genome-wide linkage scans have localized common regions, possibly harboring susceptibility genes on chromosomes 1, 2, 12, and 20. Variability in linkage findings underscores the probable genetic heterogeneity of type 2 diabetes. Thus, we conducted a genome scan of diabetes status using maximum likelihood methods that model affection status by a liability threshold model. Hypertensive sibships and their offspring and/or parents in the Hypertension Genetic Epidemiology Network study were recruited from five field centers. The diabetes phenotype was derived using the World Health Organization criteria and adjusted for race/study center, age, age2, sex, and with and without percent body fat. In total, 567 diabetic participants were identified in 437 families. Variance component linkage analysis was performed among 1,545 Caucasians and 1,608 African Americans using race-specific marker allele frequencies. We detected a quantitative trait loci (QTLs) influencing diabetes variance (logarithm of odds = 3.4) on chromosome 22, which overlaps a positive type 2 diabetes finding among Canadian Oji-Cree Indians. We also observed suggestive evidence for linkage on chromosomes 1, 2, 5, 8, 14, 17, and 19. The identification and replication of type 2 diabetes QTLs will bring us closer to the detection of functional genes that influence diabetes susceptibility.

Chromosome Mapping↗

PubMed2003

Associations of weight loss and changes in fat distribution with the remission of hypertension in a bi-ethnic cohort: the Atherosclerosis Risk in Communities Study.

BACKGROUND: To examine associations of weight loss and changes in fat distribution with changes in blood pressure and the remission of hypertension in a community-based sample. METHODS: Participants were 3245 white and African-American men and women, 45-64 years of age, who participated in the Atherosclerosis Risk in Communities Study over an average of 9 years. Mixed models analyses were used to examine the associations of weight loss and changes in fat distribution with changes in blood pressure. Proportional hazard models with time-dependent covariates were used to examine the associations of weight loss and changes in fat distribution with the remission of hypertension. RESULTS: Weight loss was associated with a decrease in systolic blood pressure and diastolic blood pressure and with an increased rate of remission of hypertension. Hazard ratios of the remission of hypertension associated with 1-kg increment in annual weight loss were 2.04 (95% confidence interval [CI]: 1.62-2.59), 1.38 (95% CI: 1.14-1.67), 1.84 (95% CI: 1.47-2.29), and 1.53 (95% CI: 1.14-2.05) for white women, African-American women, white men, and African-American men, respectively. Changes in fat distribution were associated with the remission of hypertension in younger (45-54 years) participants. CONCLUSIONS: Weight loss was associated with a decrease in blood pressure and with remission of hypertension in white and African-American men and women.

Black or African American↗

PubMed2003

Associations of aging and birth cohort with body mass index in a biethnic cohort.

OBJECTIVE: To examine associations of aging and birth cohort with body mass index (BMI) in a biethnic cohort. RESEARCH METHODS AND PROCEDURES: This was a longitudinal closed cohort study of 14,500 white and African-American men and women, 45 to 64 years of age, followed for 9 years. Aging was defined as the length of the interval in years between baseline and following visits. Birth cohort was defined by the year in which participants were born. Mixed model analyses were used to examine associations of aging, birth cohort, and BMI in four ethnicity-gender groups. RESULTS: We found that aging was associated with an increase in BMI in white and African-American men and women. The associations between aging and BMI were stronger in the younger birth cohorts. Except for white women, younger birth cohort was associated with a higher BMI. After adjusting for aging, birth cohort was associated with an increase in BMI of 0.1 kg/m(2) [95% confidence interval (95% CI): -0.1, 0.3] among white women. The corresponding values for African-American women, white men, and African-American men are 0.5 kg/m(2) (95% CI: 0.1, 0.9), 0.6 kg/m(2) (95% CI: 0.4, 0.8), and 0.6 kg/m(2) (95% CI: 0.2, 1.0), respectively. DISCUSSION: Our analyses show that, in all except white women, people in this age range who were born later have a higher BMI at the same attained age. In all groups, people who are born later gained more weight as they aged. In general, subjects ages 45 to 64 years gained weight as they aged 9 years.

Aged↗

PubMed2003

Twin study of age-related macular degeneration.

PURPOSE: To evaluate the genetic contribution in age-related macular degeneration (ARMD) by a disease-ascertained twin study. METHODS: Concordance rates for ARMD in 25 twins were obtained by using four masked graders to confirm the diagnosis of ARMD and place subjects in one of three categories; concordant, intermediate, or discordant. Demographic features and known risk factors for ARMD were compared between monozygotic and dizygotic twin pairs. RESULTS: Of the 25 twin pairs, 15 were monzygotic and 10 were dizygotic. All 15 monozygotic twins were concordant or intermediate for ARMD. Of the dizygotic twin pairs, only one was concordant and five were discordant. In the demographic and risk factor analysis no unusual contributing or confounding variables were detected. CONCLUSIONS: The association between zygosity and concordance for ARMD suggests a major importance for genetics in the etiology of ARMD. Our data further support a multi-factorial, primarily polygenic etiology for the condition.

Aged↗

PubMed2002

Socioeconomic disadvantage and change in blood pressure associated with aging.

BACKGROUND: Few studies have examined how the longitudinal change in blood pressure associated with aging differs across social groups within industrialized countries. METHODS AND RESULTS: Data from the Atherosclerosis Risk In Communities Study were used to investigate differences in the incidence of hypertension and in aging-related changes in blood pressure by neighborhood and individual socioeconomic factors over a 9-year follow-up. Disadvantage in multiple socioeconomic dimensions was associated with the greatest risk of developing hypertension (age- and sex-adjusted hazard ratio [HR] and 95% CI: HR 1.95, 95% CI 1.38 to 2.75 in whites and HR 1.43, 95% CI 0.96 to 2.13 in blacks). Aging-related increases in systolic blood pressure were inversely associated with socioeconomic position in whites (mean [SEM] 5-year increase in systolic blood pressure 7 [0.7] mm Hg in the most disadvantaged category and 5.4 [0.4] mm Hg in the most advantaged category). In whites, low socioeconomic position was also associated with more rapid declines in diastolic blood pressure after 50 years of age. Socioeconomic differences in hypertension incidence and changes in systolic blood pressure were reduced after adjustment for baseline blood pressure. CONCLUSION: The change in blood pressure associated with aging varies by social groups within the United States.

Black or African American↗

PubMed2002

Pulse pressure and age at menopause.

BACKGROUND: The objective of this study was to study the association of early age at menopause with pulse pressure (PP), a marker of arterial stiffness, and PP change. METHODS: The effect of natural menopause was studied in 2484 women from the Atherosclerosis Risk in Communities (ARIC) Study who had not used hormone replacement therapy and who had not had a hysterectomy. The cross-sectional association of age with PP was evaluated in the entire cohort. The cross-sectional association of recalled age at menopause was evaluated in the 1688 women who were postmenopausal at baseline. PP change over 6 years was assessed in relation to menopausal age separately in women who were postmenopausal at baseline and in those whose menopause occurred during the 6-year interval. RESULTS: Chronological age was strongly and positively associated with PP in cross-sectional analyses, but not independently associated with PP change. While menopausal age was not associated cross-sectionally with PP, early age at menopause (age<45) was significantly and independently associated with a slightly larger increase in PP (8.4, 95% CI 7.0-9.8) than later menopause (6.5, 95% CI 5.8;7.2). However, among normotensive women the difference was not statistically significant (p = 0.07, 6.1 vs 4.7). CONCLUSIONS: Early age at menopause may be related to a greater increase in arterial stiffness, but the effect appears to be small and further evidence is needed.

Journal Article↗