Walter Palmas

A Randomized Trial Comparing Telemedicine Case Management with Usual Care in Older, Ethnically Diverse, Medically Underserved Patients with Diabetes Mellitus

BACKGROUND Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of illness. METHODS The authors conducted a randomized, controlled trial comparing telemedicine case management to usual care, with blinding of those obtaining outcome data, in 1,665 Medicare recipients with diabetes, aged 55 years or greater, and living in federally designated medically underserved areas of New York State. The primary endpoints were HgbA1c, blood pressure, and low-density lipoprotein (LDL) cholesterol levels. RESULTS In the intervention group (n = 844), mean HgbA1c improved over one year from 7.35% to 6.97% and from 8.35% to 7.42% in the subgroup with baseline HgbA1c > or =7% (n = 353). In the usual care group (n = 821) mean HgbA1c improved over one year from 7.42% to 7.17%. Adjusted net reductions (one-year minus baseline mean values in each group, compared between groups) favoring the intervention were as follows: HgbA1c, 0.18% (p = 0.006), systolic and diastolic blood pressure, 3.4 (p = 0.001) and 1.9 mm Hg (p < 0.001), and LDL cholesterol, 9.5 mg/dL (p < 0.001). In the subgroup with baseline HgbA1c > or =7%, net adjusted reduction in HgbA1c favoring the intervention group was 0.32% (p = 0.002). Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York. CONCLUSION Telemedicine case management improved glycemic control, blood pressure levels, and total and LDL cholesterol levels at one year of follow-up.

A Randomized Trial Comparing Telemedicine Case Management with Usual Care in Older, Ethnically Diverse, Medically Underserved Patients with Diabetes Mellitus: 5 Year Results of the IDEATel Study

CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care. OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older, ethnically diverse, medically underserved patients with diabetes. DESIGN, Setting, and Patients A randomized controlled trial was conducted, comparing telemedicine case management to usual care, with blinded outcome evaluation, in 1,665 Medicare recipients with diabetes, aged >/= 55 years, residing in federally designated medically underserved areas of New York State. Interventions Home telemedicine unit with nurse case management versus usual care. Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c (HgbA1c), low density lipoprotein (LDL) cholesterol, and blood pressure levels. RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints (HgbA1c, p = 0.001; LDL, p < 0.001; systolic and diastolic blood pressure, p = 0.024; p < 0.001). Estimated differences (95% CI) in year 5 were 0.29 (0.12, 0.46)% for HgbA1c, 3.84 (-0.08, 7.77) mg/dL for LDL cholesterol, and 4.32 (1.93, 6.72) mm Hg for systolic and 2.64 (1.53, 3.74) mm Hg for diastolic blood pressure. There were 176 deaths in the intervention group and 169 in the usual care group (hazard ratio 1.01 [0.82, 1.24]). CONCLUSIONS Telemedicine case management resulted in net improvements in HgbA1c, LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries. Mortality was not different between the groups, although power was limited. Trial Registration http://clinicaltrials.gov Identifier: NCT00271739.

Columbia University's Informatics for Diabetes Education and Telemedicine (IDEATel) Project: rationale and design.

The Columbia University Informatics for Diabetes Education and Telemedicine (IDEATel) Project is a four-year demonstration project funded by the Centers for Medicare and Medicaid Services with the overall goals of evaluating the feasibility, acceptability, effectiveness, and cost-effectiveness of telemedicine in the management of older patients with diabetes. The study is designed as a randomized controlled trial and is being conducted by a state-wide consortium in New York. Eligibility requires that participants have diabetes, are Medicare beneficiaries, and reside in federally designated medically underserved areas. A total of 1,500 participants will be randomized, half in New York City and half in other areas of the state. Intervention participants receive a home telemedicine unit that provides synchronous videoconferencing with a project-based nurse, electronic transmission of home fingerstick glucose and blood pressure data, and Web access to a project Web site. End points include glycosylated hemoglobin, blood pressure, and lipid levels; patient satisfaction; health care service utilization; and costs. The project is intended to provide data to help inform regulatory and reimbursement policies for electronically delivered health care services.

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

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.

Cystatin C Identifies Chronic Kidney Disease Patients at Higher Risk for Complications

Although cystatin C is a stronger predictor of clinical outcomes associated with CKD than creatinine, the clinical role for cystatin C is unclear. We included 11,909 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) and assessed risks for death, cardiovascular events, heart failure, and ESRD among persons categorized into mutually exclusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR <60 ml/min per 1.73 m(2)): creatinine only, cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9% had CKD by the creatinine-based equation only, 2% had CKD by the cystatin C-based equation only, and 4% had CKD by both equations; in CHS, these percentages were 12, 4, and 13%, respectively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95% CI 0.50 to 1.26) for CKD by creatinine only; 3.23 (95% CI 1.84 to 5.67) for CKD by cystatin C only; and 1.93 (95% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95% CI 0.98 to 1.21), 1.78 (95% CI 1.53 to 2.08), and 1.74 (95% CI 1.58 to 1.93), respectively. The pattern was similar for cardiovascular disease (CVD), heart failure, and kidney failure outcomes. In conclusion, among adults diagnosed with CKD using the creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD according to the cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for complications.

Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.

Glycemic Control and Health Disparities in Older Ethnically Diverse Underserved Adults With Diabetes: Five-year results from the Informatics for Diabetes Education and Telemedicine (IDEATel) study

OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Differences in kidney function and incident hypertension: The multi-ethnic study of atherosclerosis

Context Evidence about whether early kidney dysfunction predates hypertension is scant. Contribution In this study, 2767 adults who were middle-aged or older and did not have clinically recognized hypertension or kidney or cardiovascular disease at baseline were followed for about 3 years. About 20% developed hypertension. Higher baseline levels of cystatin C were associated with higher incidence of hypertension, independent of other risk factors. Spot baseline measures of the urinary albumincreatinine ratio were not associated with hypertension incidence, independent of other risk factors. Implication Early renal impairment marked by higher cystatin C levels may play a role in the pathogenesis of hypertension. The Editors The kidneys play a central role in the regulation of blood pressure (1, 2). Although most individuals with established kidney disease have hypertension, the direction of the association between kidney dysfunction and elevated blood pressure remains controversial (37). Evidence suggests that early disturbances in kidney function may contribute to the development of hypertension. Transplantation of kidneys from Dahl and other hypertensive rat species transfers hypertension to recipient animals (8). Renal ischemia in early stages of kidney disease stimulates the reninangiotensinaldosterone and sympathetic nervous systems, which promotes sodium retention and increase peripheral resistance (9, 10). Evidence links low birthweight, a surrogate marker for reduced nephron number, with a greater risk for hypertension later in life (11). Accident victims with essential hypertension have a documented decrease in nephron number compared with matched control participants (12). The evaluation of early differences in kidney function has been hampered by the imprecision of traditional serologic methods and estimating equations (13). Cystatin C is an alternative marker of kidney function. It correlates with formal measurements of glomerular filtration and is more precise than serum creatinine levels in detecting early kidney dysfunction (14, 15). Urinary albumin excretion is a complementary marker to renal filtration and partially reflects hemodynamic disturbances within the glomerulus. We evaluated serum cystatin C levels and the urinary albumincreatinine ratio separately and in combination as predictors of incident hypertension in a multiethnic, community-based cohort without clinically recognized kidney or cardiovascular disease. Methods Study Population The MESA (Multi-Ethnic Study of Atherosclerosis) is a community-based study of subclinical cardiovascular disease among 6814 adults age 45 to 84 years (16). Between 2000 and 2002, the MESA researchers recruited participants from 6 communities: Forsyth County, North Carolina; northern Manhattan and Bronx, New York; the city of Baltimore and Baltimore County, Maryland; St. Paul, Minnesota; Chicago, Illinois; and Los Angeles County, California. The MESA researchers sampled eligible participants by self-reported race or ethnicity to create a cohort that was 38% white; 28% African American; 22% Hispanic; and 12% Asian, primarily of Chinese descent. The MESA researchers excluded participants if they had a previous diagnosis of cardiovascular disease (that is, physician-diagnosed heart attack, angina, stroke, transient ischemic attack, heart failure, or atrial fibrillation; were taking nitroglycerin; or had had angioplasty, coronary artery bypass grafting, valve replacement, pacemaker or defibrillator implantation, or any surgery on the heart or arteries.) We excluded MESA participants with baseline hypertension from our current analysis. Baseline hypertension was defined by any of the following criteria: systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, the use of medication for hypertension, or a self-reported history of hypertension. To focus the analyses on clinically unrecognized differences in kidney function, we excluded participants with clinical kidney disease, defined as an estimated glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m2, or microalbuminuria, defined as a urinary albumincreatinine ratio of at least 25 mg/g for women or 17 mg/g for men (17, 18). We calculated estimated GFR by using the 4-variable Modification of Diet in Renal Disease equation (19). Participants with an estimated GFR greater than 90 mL/min per 1.73 m2 were examined separately in sensitivity analyses. Finally, we excluded participants who did not return for any follow-up MESA examinations. Figure 1 shows a flow diagram of the study participants. Figure 1. Study flow diagram. GFR = glomerular filtration rate; MESA = Multi-Ethnic Study of Atherosclerosis. Ascertainment of Exposure Variables The Laboratory for Clinical Biochemistry Research (University of Vermont, Burlington, Vermont) measured baseline cystatin C by using the BN II nephelometer (Dade Behring, Deerfield, Illinois) (20) and measured baseline urinary albumincreatinine ratio on a single spot morning collection by using nephelometry and the rate-Jaffe reaction, respectively. The coefficient of variation for cystatin C is 7.7%; cystatin C levels are stable through multiple freezethaw cycles (21). We reported the urinary albumincreatinine ratio as milligrams of albumin per gram of creatinine, which correlates with milligrams of albumin obtained from a 24-hour urine collection (22, 23). Studies have suggested that urinary albumincreatinine ratio values are higher in women because of lower creatinine excretion; therefore, we analyzed the values as sex-specific quartiles (18). Ascertainment of Outcome The MESA personnel assessed blood pressure and medication use during each MESA examination, each of which was conducted 18 months apart. They obtained 3 seated blood pressure measurements 5 minutes apart by using an automated sphygmomanometer. We calculated the mean of the second 2 measurements for analysis. The MESA personnel asked participants to bring all medications to each examination, and they assessed medication use by taking a medication inventory (24). We defined incident hypertension as systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or the use of any antihypertensive medication during the second or third MESA follow-up examination (25). Because angiotensin-converting enzyme inhibitors and angiotensin II antagonists may be prescribed to individuals with diabetes but without hypertension, sensitivity analyses explored associations after excluding participants with diabetes. We also explored a second outcome, a clinically meaningful increase in blood pressure, defined as an increase in systolic blood pressure of at least 10 mm Hg, an increase in diastolic blood pressure of at least 5 mm Hg, or the introduction of an antihypertensive medication during follow-up. Ascertainment of Covariates We assessed covariates at the MESA baseline examination. Diabetes was defined as a reported history of diabetes, the use of any diabetes medication, or a fasting blood glucose level of at least 7 mmol/L (126 mg/dL) (26). Impaired fasting glucose was defined by a fasting glucose level of 5.6 to 6.99 mmol/L (100 to 125 mg/dL) without diabetes (26). The MESA investigators used a questionnaire to obtain histories of alcohol use and smoking. We analyzed smoking as the number of reported pack-years and alcohol use as the mean number of alcoholic drinks consumed per week. The MESA investigators obtained laboratory values after an 8- to 12-hour overnight fast. The Laboratory for Clinical Biochemistry Research measured high-sensitivity C-reactive protein levels by using the BN II nephelometer. Statistical Analysis We tabulated baseline participant characteristics by quartiles of cystatin C and urinary albumincreatinine ratio. We calculated risk time as the elapsed time from the baseline to the third MESA examination, unless a participant developed hypertension at the second examination or was lost to follow-up before the third examination, in which case we calculated risk time as the elapsed time from the baseline to the second examination. We calculated unadjusted hypertension rates as the number of events divided by person-years at risk, and we examined hypertension rates according to race or ethnicity, sex, and quartiles of cystatin C and urinary albumincreatinine ratio. We used Poisson (log-link) regression to model the incidence rate ratio of hypertension as a function of predictor covariates with robust variance estimation and an offset for follow-up time (27). We selected a 15-nmol/L increment in cystatin C levels for continuous analyses because it corresponded approximately to the intraquartile range for cystatin C. Variables that might be related to kidney function or hypertension were selected a priori (Table 1) and were added in blocks to progressive nested models. We used a Wald test to calculate P values and 95% CIs for model covariates and to evaluate the statistical significance of interactions. We used complete case analysis to handle missing data. Table 1. Baseline Characteristics, by Serum Cystatin C Level Searching MEDLINE from July 2007 through January 2008 did not yield any new references to the relationship of cystatin C levels with incident hypertension. Role of the Funding Source This study was supported by contracts from the National Heart, Lung, and Blood Institute and by a National Institutes of Health Career Development Award. The National Heart, Lung, and Blood Institute played a role in data collection, data management, and review and approval of the manuscript. Results Of the 6814 MESA participants, we excluded 3508 because of baseline hypertension, 151 because of an estimated GFR less than 60 mL/min per 1.73 m2, and 182 because of microalbuminuria (Figure 1). In addition, we excluded 43 participants because of a missing cystatin C value or urinary albumincreatinine ratio, 1 for an implausible cystatin C valu

Combined admixture mapping and association analysis identifies a novel blood pressure genetic locus on 5p13: contributions from the CARe consortium

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 [Womens 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.

Association between language and risk factor levels among Hispanic adults with hypertension, hypercholesterolemia, or diabetes

BACKGROUND The association of acculturation and cardiovascular risk factor control among populations with high proportions of immigrants has not been well studied. METHODS We studied 1,492 Hispanic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with hypertension, hypercholesterolemia, and/or diabetes. We used linear regression to examine the cross-sectional relationships between acculturation measures and cardiovascular risk factor levels. Outcome measures included systolic blood pressure (mm Hg), fasting low-density lipoprotein (LDL) cholesterol (mg/dL), and fasting blood glucose (mg/dL). Covariates included education, income, health insurance, physical activity, dietary factors, risk factor-specific medication use, duration of medication use, smoking, and body mass index. RESULTS There were 580 Hispanics with hypertension, 539 with hypercholesterolemia, and 248 with diabetes. After adjustment for age and gender, Spanish-speaking Hispanics with cardiovascular risk factors had higher systolic blood pressure, fasting LDL cholesterol, and fasting blood glucose compared to English-speaking Hispanics. Differences in systolic blood pressure were accounted for mainly by education, whereas differences in LDL cholesterol were almost entirely accounted for by cholesterol-lowering medication use. Differences in fasting glucose were partly accounted for by socioeconomic variables but were augmented after adjustment for dietary factors. Similar associations were observed between proportion of life in the United States and risk factor levels. CONCLUSIONS Among those with cardiovascular risk factors, Hispanics who spoke Spanish at home and lived less time in the United States had worse control of cardiovascular risk factors. Treatment strategies that focus on Hispanics with low levels of acculturation may improve cardiovascular risk factor control.