-
[show abstract]
[hide abstract]
ABSTRACT: Objectives. We examined the social impact of the telemedicine intervention effects in lower- and higher-socioeconomic status (SES) participants in the Informatics for Diabetes Education and Telemedicine (IDEATel) study. Methods. We conducted a randomized controlled trial comparing telemedicine case management with usual care, with blinded outcome evaluation, in 1665 Medicare recipients with diabetes, aged 55 years or older, residing in federally designated medically underserved areas of New York State. The primary trial endpoints were hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol, and systolic blood pressure levels. Results. HbA1c was higher in lower-income participants at the baseline examination. However, we found no evidence that the intervention increased disparities. A significant moderator effect was seen for HbA1c (P = .004) and systolic blood pressure (P = .023), with the lowest-income group showing greater intervention effects. Conclusions. Lower-SES participants in the IDEATel study benefited at least as much as higher-SES participants from telemedicine nurse case management for diabetes. Tailoring the intensity of the intervention based on clinical need may have led to greater improvements among those not at goal for diabetes control, a group that also had lower income, thereby avoiding the potential for an innovative intervention to widen socioeconomic disparities. (Am J Public Health. Published online ahead of print March 14, 2013: e1-e7. doi:10.2105/AJPH.2012.300909).
American Journal of Public Health 03/2013; · 3.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND
Brachial pulse pressure (PP) has been found to be associated with markers of subclinical cardiovascular disease, including carotid intima-media thickness and left-ventricular mass index (LVMI), but it is unclear whether these associations are independent of traditional cardiovascular risk factors and of the steady, nonpulsatile component of blood pressure (BP). Moreover, it is unknown whether these associations are modified by gender, age, or race/ethnicity.METHODS
We used multivariate linear regression models to assess the relationship between brachial PP and three markers of subclinical cardiovascular disease (CVD) (common carotid intima-media thickness (CC-IMT), internal carotid intima-media thickness (IC-IMT), and LVMI) in four race/ethnic groups in the Multi-Ethnic Study of Atherosclerosis. The models were adjusted for traditional Framingham risk factors (age, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, diabetes, smoking status), use of lipid-lowering medication, use of antihypertensive medication, study site, and mean arterial pressure (MAP).RESULTSThe assessment was done on 6,776 participants (2,612 non-Hispanic white, 1,870 African-American, 1,494 Hispanic, and 800 Chinese persons). The associations between brachial PP and CC-IMT, IC-IMT, and LVMI were significant in fully adjusted models. The three subclinical markers also showed significant interactions with gender (P < 0.0001), with stronger interactions in men. There was an interaction with age for LVMI (P = 0.004) and IC-IMT (P = 0.008). Race/ethnicity modified the association of PP with CC-IMT.CONCLUSIONS
Brachial PP was independently associated with subclinical CVD after adjustment for cardiovascular risk factors and mean arterial pressure (MAP). The strength of the association differed significantly for strata of gender, age, and race/ethnicity.
American Journal of Hypertension 02/2013; · 3.18 Impact Factor
-
Santhi K Ganesh,
Vinicius Tragante,
Wei Guo,
Yiran Guo,
Matthew B Lanktree,
Erin N Smith,
Toby Johnson,
Berta Almoguera Castillo,
John Barnard,
Jens Baumert, [......],
Pim van der Harst,
Yvonne T van der Schouw,
Nilesh J Samani,
Andrew D Johnson,
Patricia B Munroe,
Paul I W de Bakker,
Xiaofeng Zhu,
Daniel Levy,
Brendan J Keating,
Folkert W Asselbergs
[show abstract]
[hide abstract]
ABSTRACT: Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 single nucleotide polymorphisms (SNPs) that capture variation in ∼2,100 candidate genes for cardiovascular phenotypes in 61,619 individuals of European ancestry from cohort studies in the US and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed ten previously known loci associated with SBP, DBP, MAP, or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P value<2.4 x 10(-6)). We then replicated these associations in an independent set of 65,886 individuals of European ancestry. Findings from eQTL analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease, left ventricular hypertrophy, or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
Human Molecular Genetics 01/2013; · 7.64 Impact Factor
-
Jasmin Divers,
Nicholette D Palmer,
Lingyi Lu,
Thomas C Register,
J Jeffrey Carr,
Pamela J Hicks,
R Caresse Hightower,
S Carrie Smith,
Jianzhao Xu,
Amanda J Cox, [......],
Kathleen F Kerr,
Y-D Ida Chen, Walter Palmas,
Jerome I Rotter,
Christina L Wassel,
Alain Bertoni,
David Herrington,
Lynne E Wagenknecht,
Carl D Langefeld,
Barry I Freedman
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: -The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping (AM) may be informative for identifying genetic variants associated with subclinical cardiovascular disease (CVD). METHODS AND RESULTS: -AM of CAC was performed in 1,040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study (AA-DHS), Multi-Ethnic Study of Atherosclerosis (MESA), and Family Heart Study (FamHS) using the Illumina custom ancestry informative marker (AIM) panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each AIM, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each AIM using these probabilities and CAC, accounting for global ancestry, age, gender and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, LOD=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0) and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, while markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1,350 AAs without diabetes and 2,497 diabetic European Americans from MESA and the Diabetes Heart Study. CONCLUSIONS: -Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical CVD.
Circulation Cardiovascular Genetics 12/2012; · 6.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the association between serum adiponectin level and all-cause mortality in people with type 2 diabetes. Because of the insulin-sensitizing, anti-inflammatory, and antiatherogenic effects of adiponectin, we hypothesized that higher adiponectin level would be associated with lower all-cause mortality.
A total of 609 men and women aged 72 ± 6.3 years with type 2 diabetes and information on total and high molecular weight adiponectin were followed for a median of 5 years. The longitudinal association between adiponectin and all-cause mortality was analyzed with Cox proportional hazards models with time from adiponectin measurement to death as the time-to-event variable. Analyses were adjusted for demographic variables and significant diabetes parameters, significant cardiovascular parameters, and significant diabetes medications.
Total and high molecular weight adiponectin were highly correlated. The highest adiponectin quartile was strongly associated with higher all-cause mortality compared with the lowest quartile (hazard ratio = 4.0 [95% CI: 1.7-9.2]) in the fully adjusted model. These results did not change in analyses stratified by sex and thiazolidinedione use, after exclusion of people who died within one year of adiponectin measurement, or when change in weight before adiponectin measurement was considered.
Contrary to our hypothesis, higher adiponectin level was related to higher all-cause mortality. This association was not explained by confounding by other characteristics, including medications or preceding weight loss.
Diabetes care 07/2012; 35(9):1858-63. · 8.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objectives. Adherence to diabetes self care is poor for Hispanic American and African-American patients. This study examined the change in adherence over time and in response to a telemedicine intervention for elderly diabetes patients in these groups compared to white diabetes patients. We also examined whether adherence mediated the effect of the intervention on glycemic control (A1c). Design. The Informatics for Diabetes Education and Telemedicine project randomized medically underserved Medicare patients (n=1665) to telemedicine case management (televideo educator visits, individualized goal-setting/problem solving) or usual care. Hispanic and African-American educators delivered the intervention in Spanish if needed. Main outcome measures. Annual assessment included A1c and self-reported adherence (Summary of Diabetes Self-Care Activities scale). A simple model (only time and group terms) and a model with covariates (e.g., age) were examined for baseline and 5 years of follow-up. SAS PROC Mixed was used with non-linear terms to examine mediating effects of adherence on A1c, by performing tests of the mediating path coefficients. Results. Over time, self-reported adherence improved for the treatment group compared to usual care (p<0.001). There was no significant interaction with racial/ethnic group membership, i.e., all groups improved. However, minority subjects were consistently less adherent than whites. Also, greater comorbidity and diabetes symptoms predicted poorer adherence, greater duration of diabetes and more years of education predicted better adherence. Adherence was a significant mediator of A1c (p<0.001). Conclusions. A unique, tailored telemedicine intervention was effective in achieving improved adherence to diabetes self care. However, African-American and Hispanic American participants were less adherent than white participants at all time points despite an individualized and accessible intervention. The finding that adherence did mediate glycemic control suggests that unique interventions for minority groups may be needed to overcome this disparity.
Ethnicity and Health 07/2012; · 1.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based setting.
Prospective observational study.
4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C-based estimate of glomerular filtration rate (eGFR(cys)) >60 mL/min/1.73 m(2) and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry.
We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and d-dimer levels with kidney function decrease.
Kidney function decrease was assessed primarily by repeated measurements of eGFR(cys) over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m(2) per year. Incident low eGFR was defined as the onset of eGFR(cys) <60 mL/min/1.73 m(2) at any follow-up examination and eGFR(cys) decrease ≥1 mL/min/1.73 m(2) per year.
Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFR(cys) was 96 mL/min/1.73 m(2) and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation [SD] of biomarker) had the strongest association with kidney function decrease (β = -0.25; 95% CI, -0.38 to -0.12; P < 0.001), followed by IL-6 (β = -0.16; 95% CI, -0.29 to -0.03; P = 0.01), CRP (β = -0.09; 95% CI, -0.22 to 0.03; P = 0.1), and fibrinogen levels (β = -0.09; 95% CI, -0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19).
Observational study design and absence of measured GFR.
Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease.
American Journal of Kidney Diseases 05/2012; 60(2):225-32. · 5.43 Impact Factor
-
Ani Manichaikul, Walter Palmas,
Carlos J Rodriguez,
Carmen A Peralta,
Jasmin Divers,
Xiuqing Guo,
Wei-Min Chen,
Quenna Wong,
Kayleen Williams,
Kathleen F Kerr,
Kent D Taylor,
Michael Y Tsai,
Mark O Goodarzi,
Michèle M Sale,
Ana V Diez-Roux,
Stephen S Rich,
Jerome I Rotter,
Josyf C Mychaleckyj
[show abstract]
[hide abstract]
ABSTRACT: Using ~60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By projection of principal components (PCs) of ancestry to samples from the HapMap phase III and the Human Genome Diversity Panel (HGDP), we show the first two PCs quantify the Caucasian, African, and Native American origins, while the third and fourth PCs bring out an axis that aligns with known South-to-North geographic location of HGDP Native American samples and further separates MESA Mexican versus Central/South American samples along the same axis. Using k-means clustering computed from the first four PCs, we define four subgroups of the MESA Hispanic cohort that show close agreement with self-identification, labeling the clusters as primarily Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. To demonstrate our recommendations for genetic analysis in the MESA Hispanic cohort, we present pooled and stratified association analysis of triglycerides for selected SNPs in the LPL and TRIB1 gene regions, previously reported in GWAS of triglycerides in Caucasians but as yet unconfirmed in Hispanic populations. We report statistically significant evidence for genetic association in both genes, and we further demonstrate the importance of considering population substructure and genetic heterogeneity in genetic association studies performed in the United States Hispanic population.
PLoS Genetics 04/2012; 8(4):e1002640. · 8.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The relationship of infections and glycemic control in diabetes has been previously investigated but no solid findings have been described. Meanwhile, the detection of any infection at the early stages of disease progression, i.e. during the incubation period, is critical. In order to study this topic, we used the infection evidence and the daily glycemic control data of 248 type-2 diabetics who participated in a large telemedicine study. The results showed that morning blood glucose was significantly elevated and that diabetics performed the measurements at a later time when infected. A simple model for predicting the occurrence of infection based on the glycemic control variables showed good performance (sensitivity: 56%, specificity: 92%). A set of variables that synthesize a diabetic's profile could be included in a dedicated model and facilitate the early detection of infections; other aspects, such as continuous self-monitoring and personalized medical records, should be examined in this direction.
Health Informatics Journal 03/2012; 18(1):26-35. · 1.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE: Hispanics in the USA are affected by the diabetes epidemic disproportionately, and they consistently have lower access to care, poorer control of the disease and higher risk of complications. This study evaluates whether a community health worker (CHW) intervention may improve clinically relevant markers of diabetes care in adult underserved Hispanics. METHODS AND ANALYSIS: The Northern Manhattan Diabetes Community Outreach Project (NOCHOP) is a two-armed randomised controlled trial to be performed as a community-based participatory research study performed in a Primary Care Setting in Northern Manhattan (New York City). 360 Hispanic adults with poorly controlled type 2 diabetes mellitus (haemoglobin A1c >8%), aged 35-70 years, will be randomised at a 1:1 ratio, within Primary Care Provider clusters. The two study arms are (1) a 12-month CHW intervention and (2) enhanced usual care (educational materials mailed at 4-month intervals, preceded by phone calls). The end points, assessed after 12 months, are primary = haemoglobin A1c and secondary = blood pressure and low-density lipoprotein-cholesterol levels. In addition, the study will describe the CHW intervention in terms of components and intensity and will assess its effects on (1) medication adherence, (2) medication intensification, (3) diet and (4) physical activity. ETHICS AND DISSEMINATION: All participants will provide informed consent; the study protocol has been approved by the Institutional Review Board of Columbia University Medical Center. CHW interventions hold great promise in improving the well-being of minority populations who suffer from diabetes mellitus. The NOCHOP study will provide valuable information about the efficacy of those interventions vis-à-vis clinically relevant end points and will inform policy makers through a detailed characterisation of the programme and its effects. CLINICAL TRIAL REGISTRATION NUMBER: NCT00787475 at clinicaltrials.gov.
BMJ open. 01/2012; 2(2):e001051.
-
Carmen A Peralta,
David R Jacobs,
Ronit Katz,
Joachim H Ix,
Magdalena Madero,
Daniel A Duprez,
Mark J Sarnak,
Michael H Criqui,
Holly J Kramer, Walter Palmas,
David Herrington,
Michael G Shlipak
[show abstract]
[hide abstract]
ABSTRACT: The association of subclinical vascular disease and early declines in kidney function has not been well studied.
Prospective cohort study.
Multi-Ethnic Study of Atherosclerosis (MESA) participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) with follow-up of 5 years.
Pulse pressure, small (SAE) and large arterial elasticity (LAE), and flow-mediated dilation.
Kidney function decline.
SAE and LAE were measured by pulse contour analysis of the radial artery. Kidney function was assessed by eGFR based on serum creatinine (eGFR(SCr)) and cystatin C (eGFR(SCysC)).
For 4,853 adults, higher pulse pressure and lower SAE and LAE had independent and linear associations with faster rates of kidney function decline. Compared with persons with pulse pressure of 40-50 mm Hg, eGFR(SCysC) declines were 0.29 (P = 0.006), 0.56 (P < 0.001), and 0.91 (P < 0.001) mL/min/1.73 m(2)/y faster in persons with pulse pressure of 50-60, 60-70, and >70 mm Hg, respectively. Compared with the highest quartile of SAE (most elastic), eGFR(SCysC) declines were 0.26 (P = 0.009), 0.35 (P = 0.001), and 0.70 (P < 0.001) mL/min/1.73 m(2)/y faster for the second, third, and fourth quartiles, respectively. For LAE, compared with the highest quartile, eGFR(SCysC) declines were 0.28 (P = 0.004), 0.58 (P < 0.001), and 0.83 (P < 0.001) mL/min/1.73 m(2)/y faster for each decreasing quartile of LAE. Findings were similar for eGFR(SCr). In contrast, for 2,997 adults with flow-mediated dilation and kidney function measures, flow-mediated dilation was not associated significantly with kidney function decline. For every 1-standard deviation greater flow-mediated dilation, eGFR(SCysC) and eGFR(SCr) changed by 0.05 (P = 0.3) and 0.06 mL/min/1.73 m(2)/y (P = 0.04), respectively.
We had no direct measure of GFR, in common with nearly all large population-based studies.
Higher pulse pressure and lower arterial elasticity, but not flow-mediated dilation, were associated linearly and independently with faster kidney function decline in persons with eGFR ≥60 mL/min/1.73 m(2). Future studies should investigate whether treatments to decrease the stiffness of large and small arteries may slow the rate of kidney function loss.
American Journal of Kidney Diseases 01/2012; 59(1):41-9. · 5.43 Impact Factor
-
Joanne M Murabito,
Charles C White,
Maryam Kavousi,
Yan V Sun,
Mary F Feitosa,
Vijay Nambi,
Claudia Lamina,
Arne Schillert,
Stefan Coassin,
Joshua C Bis, [......],
H-Erich Wichmann,
James F Wilson,
Jacqueline C M Witteman,
Yongmei Liu,
Caroline Hayward,
Ingrid B Borecki,
Andreas Ziegler,
Kari E North,
L Adrienne Cupples,
Florian Kronenberg
[show abstract]
[hide abstract]
ABSTRACT: Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.
Continuous ABI and PAD (ABI ≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed effects inverse variance weighted meta-analyses. There were a total of 41 692 participants of European ancestry (≈60% women, mean ABI 1.02 to 1.19), including 3409 participants with PAD and with genome-wide association study data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β=-0.006, P=2.46×10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16 717). The association for rs10757269 strengthened in the combined discovery and replication analysis (P=2.65×10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, 2 previously reported candidate genes for PAD and 1 SNP associated with coronary artery disease were associated with ABI: DAB21P (rs13290547, P=3.6×10(-5)), CYBA (rs3794624, P=6.3×10(-5)), and rs1122608 (LDLR, P=0.0026).
Genome-wide association studies in more than 40 000 individuals identified 1 genome wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for coronary artery disease are associated with ABI.
Circulation Cardiovascular Genetics 12/2011; 5(1):100-12. · 6.11 Impact Factor
-
Louise V Wain,
Germaine C Verwoert,
Paul F O'Reilly,
Gang Shi,
Toby Johnson,
Andrew D Johnson,
Murielle Bochud,
Kenneth M Rice,
Peter Henneman,
Albert V Smith, [......],
Vilmundur Gudnason,
Christopher Newton-Cheh,
Daniel Levy,
Patricia B Munroe,
Bruce M Psaty,
Mark J Caulfield,
Dabeeru C Rao,
Martin D Tobin,
Paul Elliott,
Cornelia M van Duijn
[show abstract]
[hide abstract]
ABSTRACT: Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
Nature Genetics 09/2011; 43(10):1005-11. · 35.53 Impact Factor
-
Georg B Ehret,
Patricia B Munroe,
Kenneth M Rice,
Murielle Bochud,
Andrew D Johnson,
Daniel I Chasman,
Albert V Smith,
Martin D Tobin,
Germaine C Verwoert,
Shih-Jen Hwang, [......],
Marjo-Riitta Järvelin,
Bruce M Psaty,
Gonçalo R Abecasis,
Aravinda Chakravarti,
Paul Elliott,
Cornelia M van Duijn,
Christopher Newton-Cheh,
Daniel Levy,
Mark J Caulfield,
Toby Johnson
[show abstract]
[hide abstract]
ABSTRACT: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Nature 09/2011; 478(7367):103-9. · 36.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cardiovascular disease is the leading cause of death in Argentina and the U.S. Argentina is 92% urban, with cardiovascular disease risk factor levels approximating the U.S.
The Coronary Heart Disease (CHD) Policy Model is a national-scale computer model of CHD and stroke. Risk factor data were obtained from the Cardiovascular Risk Factor Multiple Evaluation in Latin America Study (2003-04), Argentina National Risk Factor Survey (2005) and U.S. national surveys. Proportions of cardiovascular events over 2005-2015 attributable to risk factors were simulated by setting risk factors to optimal exposure levels [systolic blood pressure (SBP) 115 mm Hg, low-density lipoprotein cholesterol (LDL) 2.00 mmol/l (78 mg/dl), high-density lipoprotein cholesterol (HDL) 1.03 mmol/l (60 mg/dl), absence of diabetes, and smoking]. Cardiovascular disease attributable to body mass index (BMI) >21 kg/m² was assumed mediated through SBP, LDL, HDL, and diabetes.
Cardiovascular disease attributable to major risk factors was similar between Argentina and the U.S., except for elevated SBP in men (CHD 8% points higher in Argentine men, 6% higher for stroke). CHD attributable to BMI >21 kg/m² was substantially higher in the U.S. (men 10-11% points higher; women CHD 13-14% higher).
Projected cardiovascular disease attributable to major risk factors appeared similar in Argentina and the U.S., though elevated BMI may be responsible for more of U.S. cardiovascular disease. A highly urbanized middle-income nation can have cardiovascular disease rates and risk factor levels comparable to a high income nation, but fewer resources for fighting the epidemic.
International journal of cardiology 05/2011; 150(3):332-7. · 7.08 Impact Factor
-
Ervin R Fox,
J Hunter Young,
Yali Li,
Albert W Dreisbach,
Brendan J Keating,
Solomon K Musani,
Kiang Liu,
Alanna C Morrison,
Santhi Ganesh,
Abdullah Kutlar, [......],
Lisa W Martin,
Charles B Eaton,
Sharon L R Kardia,
Herman A Taylor,
Mark J Caulfield,
Georg B Ehret,
Toby Johnson,
Aravinda Chakravarti,
Xiaofeng Zhu,
Daniel Levy
[show abstract]
[hide abstract]
ABSTRACT: The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.
Human Molecular Genetics 03/2011; 20(11):2273-84. · 7.64 Impact Factor
-
Xiaofeng Zhu,
J H Young,
Ervin Fox,
Brendan J Keating,
Nora Franceschini,
Sunjung Kang,
Bamidele Tayo,
Adebowale Adeyemo,
Yun V Sun,
Yali Li, [......],
David Curb,
Joel N Hirschhorn,
Charles Rotimi,
Alexander Reiner,
Charles Eaton,
Jerome I Rotter,
Richard S Cooper,
Susan Redline,
Aravinda Chakravarti,
Daniel Levy
[show abstract]
[hide abstract]
ABSTRACT: Admixture mapping based on recently admixed populations is a powerful method to detect disease variants with substantial allele frequency differences in ancestral populations. We performed admixture mapping analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP), followed by trait-marker association analysis, in 6303 unrelated African-American participants of the Candidate Gene Association Resource (CARe) consortium. We identified five genomic regions (P< 0.001) harboring genetic variants contributing to inter-individual BP variation. In follow-up association analyses, correcting for all tests performed in this study, three loci were significantly associated with SBP and one significantly associated with DBP (P< 10(-5)). Further analyses suggested that six independent single-nucleotide polymorphisms (SNPs) contributed to the phenotypic variation observed in the admixture mapping analysis. These six SNPs were examined for replication in multiple, large, independent studies of African-Americans [Women's Health Initiative (WHI), Maywood, Genetic Epidemiology Network of Arteriopathy (GENOA) and Howard University Family Study (HUFS)] as well as one native African sample (Nigerian study), with a total replication sample size of 11 882. Meta-analysis of the replication set identified a novel variant (rs7726475) on chromosome 5 between the SUB1 and NPR3 genes, as being associated with SBP and DBP (P< 0.0015 for both); in meta-analyses combining the CARe samples with the replication data, we observed P-values of 4.45 × 10(-7) for SBP and 7.52 × 10(-7) for DBP for rs7726475 that were significant after accounting for all the tests performed. Our study highlights that admixture mapping analysis can help identify genetic variants missed by genome-wide association studies because of drastically reduced number of tests in the whole genome.
Human Molecular Genetics 03/2011; 20(11):2285-95. · 7.64 Impact Factor
-
Ken Sin Lo,
James G Wilson,
Leslie A Lange,
Aaron R Folsom,
Geneviève Galarneau,
Santhi K Ganesh,
Struan F A Grant,
Brendan J Keating,
Steven A McCarroll,
Emile R Mohler,
Christopher J O'Donnell, Walter Palmas,
Weihong Tang,
Russell P Tracy,
Alexander P Reiner,
Guillaume Lettre
[show abstract]
[hide abstract]
ABSTRACT: Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in ~2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P<2.0×10(-13), T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P=3.0×10(-7) in Caucasians; P=3.0×10(-7) in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the α-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P<7×10(-8), A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences.
Human Genetics 03/2011; 129(3):307-17. · 5.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Informatics for Diabetes Education and Telemedicine (IDEATel) project randomized ethnically diverse underserved older adults with diabetes to a telemedicine intervention or usual care. Intervention participants had lower A1C levels over 5 years. New analyses were performed to help better understand this difference.
IDEATel randomized Medicare beneficiaries with diabetes (n = 1,665) to receive home video visits with a diabetes educator and upload glucose levels every 4-6 weeks or usual care (2000-2007). Annual measurements included BMI, A1C (primary outcome), and completion of questionnaires. Mixed-model analyses were performed using random effects to adjust for clustering within primary care physicians.
At baseline, A1C levels (mean ± SD) were 7.02 ± 1.25% in non-Hispanic whites (n = 821), 7.58 ± 1.78% in non-Hispanic blacks (n = 248), and 7.79 ± 1.68% in Hispanics (n = 585). Over time, lower A1C levels were associated with more glucose uploads (P = 0.02) and female sex (P = 0.002). Blacks, Hispanics, and insulin-users had higher A1C levels than non-Hispanic whites (P < 0.0001). BMI was not associated with A1C levels. Blacks and Hispanics had significantly fewer uploads than non-Hispanic whites over time. Hispanics had the highest baseline A1C levels and showed the greatest improvement in the intervention, but, unlike non-Hispanic whites, Hispanics did not achieve A1C levels <7.0% at 5 years.
Racial/ethnic disparities were observed in this cohort of underserved older adults with diabetes. The IDEATel telemedicine intervention was associated with improvement in glycemic control, particularly in Hispanics, who had the highest baseline A1C levels, suggesting that telemedicine has the potential to help reduce disparities in diabetes management.
Diabetes care 02/2011; 34(2):274-9. · 8.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract Background Defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, chronic kidney disease (CKD) is strongly and independently associated with cardiovascular and overall mortality. We hypothesized that reduced kidney function would be characterized by abnormalities of hemostasis. Methods We tested cross-sectional associations between (eGFR) and multiple hemostatic markers among 6751 participants representing a broad spectrum of kidney function in the Multi-Ethnic Study of Atherosclerosis (MESA). Kidney function was measured using cystatin C (eGFRcys) or creatinine, using CKD Epidemiology Collaboration (eGFRcr). Hemostatic markers included soluble thrombomodulin (sTM), soluble tissue factor (sTF), D-Dimer, von Willebrand factor (vWF), factor VIII, plasmin-antiplasmin complex (PAP), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and fibrinogen. Associations were tested using multivariable linear regression with adjustment for demographics and comorbidities. Results In comparison to persons with eGFRcys >90 ml/min/1.73 m2, subjects with eGFRcys < 60 ml/min/1.73 m2 had adjusted levels of sTM, sTF, D-Dimer, PAP, Factor VIII, TFPI, vWF and fibrinogen that were respectively 86%, 68%, 44%, 22%, 17%, 15%, 12% and 6% higher. Subjects with eGFRcys 60-90 ml/min/1.73 m2 had adjusted levels that were respectively 16%, 14%, 12%, 6%, 6%, 6%, 11% and 4% higher (p < 0.05 for all). Percent differences were not significantly different when groups were categorized by eGFRcr. Conclusions Throughout a broad spectrum of kidney function, lower eGFR was associated with higher levels of hemostatic markers. Dysregulation of hemostasis may be a mechanism by which reduced kidney function promotes higher cardiovascular risk.
BMC Nephrology. 01/2011;
