Biomedical subjects

David Curb

Publications and source records attributed to David Curb.

12 recordsLinked to original sources

PubMed2006

Panic attacks, daily life ischemia, and chest pain in postmenopausal women.

BACKGROUND: Chest pain is a common symptom of panic attacks, but little is known about the relationship in older women among panic attacks, chest pain, and daily life ischemia. METHODS: The authors conducted a cross-sectional survey of 3063 community-dwelling, generally healthy postmenopausal women enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study in 10 clinical centers of the 40-center Women's Health Initiative. Participants, ages 50 to 79 years, completed a questionnaire about occurrence of panic attacks in the previous 6 months and underwent 24-hour ambulatory electrocardiogram monitoring (AECG); 2705 women had valid AECG recordings and panic attack questionnaires. ST depression on AECG, heart rate variability (HRV), and chest pain episodes were compared among women with and without a 6-month history of panic attack. RESULTS: There was no difference in overall prevalence of ischemic episodes during AECG between women with and without panic attacks. Women with a recent history of panic were more likely to experience chest pain during AECG after controlling for potential confounders (odds ratio [OR] = 2.01; 95% confidence interval [CI] = 1.40-2.88), including both nonischemic (OR = 1.83; 95% CI = 1.26-2.65) and ischemic chest pain (OR = 4.94; 95% CI = 1.41-17.30). Although mean HRV was lower in those with panic attacks (p = .017), this was not significant after controlling for confounders. CONCLUSIONS: Postmenopausal women with a recent history of panic attacks do not appear to have more daily life ischemia as measured by occurrence of ST depression during 24-hour monitoring, but do have more chest pain and possibly lower HRV, suggesting that even sporadic panic attacks may be related to cardiovascular risk.

Activities of Daily Living↗

PubMed2006

Incorporating endophenotypes into allele-sharing based linkage tests.

For a genetic study in which there are concordant and discordant sibpairs for a complex disease trait and the measurements of other endophenotypes/intermediate phenotypes for each of the individuals are also available, we describe an allele-sharing based multipoint linkage test that utilizes nonparametrically the additional endophenotypes/intermediate phenotypes. The usefulness of this method is evaluated in simulation studies, which show that the gain in power is influenced by not only the endophenotypic value but also the correlation between the diagnosis-based phenotype and the endophenotype. In addition to reporting p values, our method also provides an index C(E), derived from the coefficients of the weight function associated with the endophenotype in the proposed statistic, to indicate the relevance of a specific endophenotype/intermediate phenotype in the genetic study. The simulation study indicates that a larger power, in general, corresponds to a larger value of the index C(E). The index C(E) is thus suggested as a quantity to be used in the choice of endophenotypes in linkage study. Data from the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) are used to illustrate the method.

Adult↗

PubMed2006

An updated meta-analysis of genome scans for hypertension and blood pressure in the NHLBI Family Blood Pressure Program (FBPP).

A meta-analysis of the results from a multicenter genome-wide linkage study for hypertension and blood pressure (BP) based on an initial sample of 6,245 individuals was published in 2003. We report here a combined linkage analysis of hypertension and BP using the complete Family Blood Pressure Program (FBPP) dataset, which includes a total of 12,028 genotyped individuals. Genome-wide linkage analyses for hypertension and BP were first performed in each of the studied ethnic group within each network and the results were combined with a meta-analysis using a modified Fisher's method of combining P values. Our meta-analysis of genome scans for the latest FBPP dataset reveals suggestive linkage for hypertension and BP at several regions on the human genome. Strong evidence for linkage at two of these regions, 2p14 and 3p14.1, have also been published in previous meta-analyses, making them good candidate locations for susceptibility variants.

Adult↗

PubMed2006

Genome-wide linkage analysis of lipids in nondiabetic Chinese and Japanese from the SAPPHIRe family study.

BACKGROUND: Lipid levels are recognized as major risk factors for coronary heart disease (CHD). Discovery of major loci underlying quantitative lipid traits could help to elucidate the genetics of CHD. METHODS: We performed a genome-wide search for quantitative trait loci linked to lipid phenotypes in 1538 Chinese subjects (509 families) and 625 Japanese subjects (204 families) not taking lipid-lowering medications from the Stanford-Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) study. The multipoint variance-components method was used to test for linkage between marker loci and each trait by maximum likelihood methods adjusted for effects of age, age(2), gender, body mass index (BMI), smoking, alcohol drinking, physical activity, and field center. RESULTS: The highest logarithm of odds (LOD) score detected was 3.22 for logarithmically transformed HDL-cholesterol on chromosome 12 at 113 cM in Chinese subjects. This score overlaps the positive findings for HDL reported in Mexican Americans (chromosome 12 at 96 cM). Although no strong evidence for linkage was found in Japanese subjects, some modest peaks (LOD score >==1.5) were found in several regions that have been reported in other published genome scans. For example, the Japanese SAPPHIRe peak for HDL (chromosome 1 at 167 cM; LOD = 1.54) was very close to the quantitative trait loci (QTL) for HDL reported in the scan of white American HyperGEN (chromosome 1 at 159.9 cM). CONCLUSIONS: Genome-wide scan for genes influencing lipid phenotypes was conducted and we found significant linkage of HDL to a locus on chromosome 12 in Chinese subjects and no linkage signal exceeding 1.68 was found in the Japanese subjects.

Adult↗

PubMed2004

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.

CONTEXT: Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain. OBJECTIVE: To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity. INTERVENTION: Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo. MAIN OUTCOME MEASURES: The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects. RESULTS: In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years. CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

Aged↗

PubMed2004

Special populations recruitment for the Women's Health Initiative: successes and limitations.

The Women's Health Initiative (WHI) is a study designed to examine the major causes of death and disability in women. This multi-arm, randomized, controlled trial of over 160,000 post-menopausal women of varying ethnic and socioeconomic backgrounds and a goal of 20% of the study participants from minority populations is perhaps one of the most challenging recruitment efforts ever undertaken. Of the two main study arms, the Clinical Trial (CT) and the Observational Study (OS), the CT arm recruitment goal was to randomize 64,500 postmenopausal women 50-79 years of age. Women enrolled in the study will be followed for a period of 8-12 years. Ten clinical centers, out of a total of 40 throughout the United States, were selected as minority recruitment centers on the basis of their history of interaction with and access to large numbers of women from certain population subgroups. WHI enrollment began in September 1993 and ended in December 1998, resulting in the randomization and enrollment of a total of 161,856 (17.5% minority) women participants (68,135 (18.5% minority) in the CT and 93,721 (16.7%) in the OS). Within the CT arm, WHI achieved 101.7% of the goal of 48,000 participants in the Dietary Modification (DM) component, and 99.4% of the goal of 27,500 in the hormone-replacement component (HRT), with 11.8% overlap between DM and HRT. Of those who expressed initial interest in WHI, African Americans had the highest randomization yields in the DM component and Hispanics had the highest in the HRT component (15.2% and 10.2%, respectively). Overall, mass mailing was the greatest source of randomized participants. In addition, minority clinics found community outreach, personal referrals, and culturally appropriate recruitment materials particularly effective recruitment tools. For minority recruitment, our findings suggest that the key to high yield is reaching the target population through appropriate recruitment strategies and study information that get their attention. Also, once minority subjects are reached, they tend to participate.

Aged↗

PubMed2003

A genome scan for hypertension susceptibility loci in populations of Chinese and Japanese origins.

BACKGROUND: Our understanding of genes that predispose to essential hypertension is poor. METHODS: A genome-wide scan for linkage at approximately 10 cM resolution was done on 1425 sibpairs of Chinese and Japanese origins that were concordant for hypertension (N = 661), low-normal blood pressure (BP) (N = 184), or discordant for BP (N = 580). RESULTS: There was no significant evidence of linkage to a single locus in the genome. There was suggestive evidence of linkage to chromosome 10p, with a LOD score of 2.5. CONCLUSIONS: We can exclude the possibility that a single gene accounts for at least 15% of the variance in hypertension in this population.

Adult↗

PubMed2003

Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program.

A combined analysis of genome scans was performed for adult height in the NHLBI Family Blood Pressure Program. Height data were available on 6752 individuals. Linkage analysis was performed first separately for each of the eight ethnic groups in the four networks using the variance component method. To increase the power to detect the common genetic components affecting height for all the individuals, a linkage analysis was performed subsequently for the combined data set by pooling the average allele-sharing IBD () for all groups. By combining the data, we replicated evidence for a QTL influencing adult height on chromosome 7 (7q31) (LOD=2.46), which has been reported in two previous studies. Suggestive linkage (LOD>1) was found in another six regions in our combined analysis. Evidence for linkage for two of these regions (2p12, 20p11) has also been reported previously.

Adult↗

PubMed2002

High-throughput genotyping of single nucleotide polymorphisms using new biplex invader technology.

The feasibility of large-scale genome-wide association studies of complex human disorders depends on the availability of accurate and efficient genotyping methods for single nucleotide polymorphisms (SNPs). We describe a new platform of the invader assay, a biplex assay, where both alleles are interrogated in a single reaction tube. The assay was evaluated on over 50 different SNPs, with over 20 SNPs genotyped in study cohorts of over 1500 individuals. We assessed the usefulness of the new platform in high-throughput genotyping and compared its accuracy to genotyping results obtained by the traditional monoplex invader assay, TaqMan genotyping and sequencing data. We present representative data for two SNPs in different genes (CD36 and protein tyrosine phosphatase 1beta) from a study cohort comprising over 1500 individuals with high or low-normal blood pressure. In this high-throughput application, the biplex invader assay is very accurate, with an error rate of <0.3% and a failure rate of 1.64%. The set-up of the assay is highly automated, facilitating the processing of large numbers of samples simultaneously. We present new analysis tools for the assignment of genotypes that further improve genotyping success. The biplex invader assay with its automated set-up and analysis offers a new efficient high-throughput genotyping platform that is suitable for association studies in large study cohorts.

Biotechnology↗

PubMed2002

A combined analysis of genomewide linkage scans for body mass index from the National Heart, Lung, and Blood Institute Family Blood Pressure Program.

A combined analysis of genome scans for obesity was undertaken using the interim results from the National Heart, Lung, and Blood Institute Family Blood Pressure Program. In this research project, four multicenter networks of investigators conducted eight individual studies. Data were available on 6,849 individuals from four ethnic groups (white, black, Mexican American, and Asian). The sample represents the largest single collection of genomewide scan data that has been analyzed for obesity and provides a test of the reproducibility of linkage analysis for a complex phenotype. Body mass index (BMI) was used as the measure of adiposity. Genomewide linkage analyses were first performed separately in each of the eight ethnic groups in the four networks, through use of the variance-component method. Only one region in the analyses of the individual studies showed significant linkage with BMI: 3q22.1 (LOD 3.45, for the GENOA network black sample). Six additional regions were found with an associated LOD >2, including 3p24.1, 7p15.2, 7q22.3, 14q24.3, 16q12.2, and 17p11.2. Among these findings, the linkage at 7p15.2, 7q22.3, and 17p11.2 has been reported elsewhere. A modified Fisher's omnibus procedure was then used to combine the P values from each of the eight genome scans. A complimentary approach to the meta-analysis was undertaken, combining the average allele-sharing identity by descent (pi) for whites, blacks, and Mexican Americans. Using this approach, we found strong linkage evidence for a quantitative-trait locus at 3q27 (marker D3S2427; LOD 3.40, P=.03). The same location has been shown to be linked with obesity-related traits and diabetes in at least two other studies. These results (1) confirm the previously reported obesity-susceptibility locus on chromosomes 3, 7, and 17 and (2) demonstrate that combining samples from different studies can increase the power to detect common genes with a small-to-moderate effect, so long as the same gene has an effect in all samples considered.

Adult↗

PubMed2002

A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate.

Resting heart rate is significantly associated with cardiovascular morbidity and mortality. However, the extent to which resting heart rate is genetically determined is poorly understood, and no genes have been found that contribute to variation in resting heart rate. Because signaling through the beta1 adrenergic receptor is a key determinant of cardiac function, we tested whether polymorphisms in this receptor are associated with resting heart rate. A cohort of >1,000 individuals of Chinese and Japanese descent, from nuclear families, was genotyped for two polymorphisms, resulting in a serine/glycine substitution at amino acid 49 (Ser49Gly) and an arginine/glycine substitution at residue 389 (Arg389Gly), in the beta1 adrenergic receptor. For comparison, polymorphisms in the beta2 and beta3 adrenergic receptors were also evaluated. The Ser49Gly polymorphism was significantly associated (P=.0004) with resting heart rate, independent of other variables, such as body-mass index, age, sex, ethnicity, exercise, smoking, alcohol intake, hypertension status, and treatment with beta blockers. The data support an additive model in which individuals heterozygous for the Ser49Gly polymorphism had mean heart rates intermediate to those of either type of homozygote, with Ser homozygotes having the highest mean heart rate and with Gly homozygotes having the lowest. Neither the Arg389Gly polymorphism in the beta1 adrenergic receptor nor polymorphisms in the beta2 and beta3 adrenergic receptors were associated with resting heart rate. The heritability of heart rate was 39.7% +/- 7.1% (P<10-7).

Age Factors↗

PubMed2002

Clustering and heritability of insulin resistance in Chinese and Japanese hypertensive families: a Stanford-Asian Pacific Program in Hypertension and Insulin Resistance sibling study.

The clustering between hypertension and other metabolic abnormalities related to insulin resistance syndrome (IRS) has been investigated in cross-sectional and prospective studies. Offspring studies have revealed that the clustering characteristics of IRS have familial components. However, it is not known whether the clustering also occurs in siblings (sibs) with different levels of blood pressure (BP). In addition, the genetic susceptibility accounting for the clustering in hypertensive families has not been determined. Siblings with Japanese or Chinese ancestry and having either similar BP levels (concordant sibs) or different BP levels (discordant sibs) were recruited. The delta method and variance component model were applied to analyze the differences in metabolic variables between hypertension (HTN) and low BP (LBP) sibs, and to compute the polygenic heritabilities for these metabolic variables and insulin sensitivity. After adjustment for age, gender and body mass index (BMI), HTN (n=393) sibs had higher levels of triglyceride (p < 0.0001), VLDL-cholesterol (p<0.0001), fasting insulin (p < 0.05), and homeostasis model assessment of insulin resistance (HOMAir) (p < 0.05) than LBP sibs (n = 389), but there were no differences in fasting glucose or high density lipoprotein (HDL)-cholesterol. The HTN sibs also had higher plasma glucose and insulin levels at 2 h after 75 g oral glucose loading (p<0.001 and p<0.01, respectively). The heritability estimates for fasting glucose, fasting insulin and HOMAir were 0.58, 0.43 and 0.46, respectively; for triglyceride, HDL-cholesterol, and BMI they were 0.60, 0.63 and 0.54, respectively. In hypertensive families, sibs with extreme levels of BP have significant differences in IRS-associated metabolic variables. The clustering characteristics and the significance of heritability estimation for these metabolic variables indicate that IRS is familial in nature and heritable in Chinese and Japanese hypertensive families.

Adult↗