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Garg P.K.,University of Southern California | Biggs M.L.,University of Washington | Carnethon M.,Northwestern University | Ix J.H.,Nephrology Section | And 9 more authors.
Hypertension | Year: 2014

Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged ≥65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among a subset of 1899 individuals with 2 ABI measurements 6 years apart. Over a median follow-up of 13.7 years, 4632 individuals were followed up for clinical PAD, defined as revascularization or diagnosed claudication. Adult Treatment Panel III MetS was associated with both incident low ABI (risk ratio, 1.26; 95% confidence interval [CI], 1.00-1.58) and clinical PAD (hazard ratio, 1.47; 95% CI, 1.11-1.94). Incorporating C-reactive protein or fibrinogen into Adult Treatment Panel III criteria identified an additional 16% to 20% of individuals as having MetS, and both C-reactive protein-MetS and fibrinogen-MetS were associated with incident low ABI (risk ratio, 1.36; 95% CI, 1.07-1.72 and risk ratio, 1.43; 95% CI, 1.13-1.81, respectively) and clinical PAD (hazard ratio, 1.56; 95% CI, 1.17-2.08 and hazard ratio, 1.55; 95% CI, 1.17-2.07, respectively). Among Adult Treatment Panel III MetS criteria, risk of PAD was most strongly associated with hypertension. © 2013 American Heart Association, Inc.

Kizer J.R.,New York Medical College | Benkeser D.,University of Washington | Arnold A.M.,University of Washington | Mukamal K.J.,Beth Israel Deaconess Medical Center | And 9 more authors.
Circulation | Year: 2012

BACKGROUND-: Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk) and cohorts with prevalent cardiovascular disease, heart failure, or advanced age (higher risk). METHODS AND RESULTS-: In a population-based study of older adults, we examined the relationships of total and high-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: No cardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrial fibrillation (group 2); and heart failure/atrial fibrillation (group 3). We found significant differences in the associations with all-cause mortality across the groups. The association in group 1 was U-shaped; increasing levels of total adiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (hazard ratio=0.81 per 1 SD [95% confidence interval, 0.65-0.95]), but above this cut point, higher levels conferred greater risk (hazard ratio=1.19 [95% confidence interval, 1.12-1.27]). Further adjustment for diabetes mellitus or insulin resistance, protection against which has been proposed to mediate the beneficial relationships of adiponectin with outcome, attenuated the association in the lower range. There was no significant association in group 2, but in group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for group 2, and magnified the one for group 3 (hazard ratio=1.31 [1.15-1.50]). Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality. CONCLUSIONS-: Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as it relates to older adults. © 2012 American Heart Association, Inc.

Branch-Elliman W.,Boston Veterans Affairs Healthcare System | Branch-Elliman W.,Beth Israel Deaconess Medical Center | Branch-Elliman W.,Harvard University | Strymish J.,Boston Veterans Affairs Healthcare System | And 3 more authors.
Infection Control and Hospital Epidemiology | Year: 2014

background. With growing demands to track and publicly report and compare infection rates, efforts to utilize automated surveillance systems are increasing. We developed and validated a simple algorithm for identifying patients with clinical methicillin-resistant Staphylococcus aureus (MRSA) infection using microbiologic and antimicrobial variables. We also estimated resource savings. methods. Patients who had a culture positive for MRSA at any of 5 acute care Veterans Affairs hospitals were eligible. Clinical infection was defined on the basis of manual chart review. The electronic algorithm defined clinical MRSA infection as a positive non-sterile-site culture with receipt of MRSA-active antibiotics during the 5 days prior to or after the culture. results. In total, 246 unique non-sterile-site cultures were included, of which 168 represented infection. The sensitivity (43.4%-95.8%) and specificity (34.6%-84.6%) of the electronic algorithm varied depending on the combination of antimicrobials included. On multivariable analysis, predictors of algorithm failure were outpatient status (odds ratio, 0.23 [95% confidence interval, 0.10-0.56]) and respiratory culture (odds ratio, 0.29 [95% confidence interval, 0.13-0.65]). The median cost was $2.43 per chart given 4.6 minutes of review time per chart. conclusions. Our simple electronic algorithm for detecting clinical MRSA infections has excellent sensitivity and good specificity. Implementation of this electronic system may streamline and standardize surveillance and reporting efforts. © 2014 by The Society for Healthcare Epidemiology of America. All rights reserved.

Laugsand L.E.,Norwegian University of Science and Technology | Laugsand L.E.,Harvard University | Ix J.H.,Nephrology Section | Ix J.H.,University of California at San Diego | And 18 more authors.
Atherosclerosis | Year: 2015

Background and aims: Fetuin-A has a plausible role in the inhibition of arterial calcification, but its association with risk of coronary heart disease (CHD) in the general population is unclear. We used two common genetic variants in the fetuin-A gene (AHSG) that are strongly associated with circulating fetuin-A levels to investigate the associations with risk of CHD and subclinical cardiovascular measures (intima-media thickness, ankle-arm index, and coronary artery calcification). Methods: Genetic variation and fetuin-A levels were assessed in 3299 community-living individuals (2733 Caucasians and 566 African Americans) 65 years of age or older, free of previous cardiovascular disease, who participated in the Cardiovascular Health Study (CHS) in 1992-1993. Results: Among Caucasians, both rs2248690 and rs4917 were associated with 12% lower fetuin-A concentrations per minor allele (P < 0.0001). The hazard ratios (HRs) per minor allele for incident CHD were 1.12 (95% CI: 1.00-1.26) for rs2248690 and 1.02 (0.91-1.14) for rs4917. Using both genotypes as an instrumental variable for measured fetuin-A, the HRs for one standard deviation increase in genetically determined fetuin-A levels on CHD risk were 0.84 (95% CI: 0.70-1.00) for rs2248690 and 0.97 (95% CI: 0.82-1.14) for rs4917, respectively. However, in CHS neither of the genotypes were associated with subclinical cardiovascular measures and when CHS data were meta-analyzed with data from six other prospective studies (totaling 26,702 Caucasian participants and 3295 CHD cases), the meta-analyzed HRs for incident CHD were 1.12 (0.93-1.34) and 1.06 (0.93-1.20) for rs2248690 and rs4917, respectively (p heterogeneity 0.005 and 0.0048). Conclusion: Common variants in the AHSG gene are strongly associated with fetuin-A levels, but their concurrent association with CHD risk in current prospective studies is inconsistent. Further investigation in studies with measured fetuin-A and AHSG variants is needed to clarify the potential causal association of fetuin-A with CHD risk. © 2015 Elsevier Ireland Ltd.

Girnius S.,Boston Veterans Affairs Healthcare System | Girnius S.,Boston Medical Center | Munshi N.C.,Boston Veterans Affairs Healthcare System | Munshi N.C.,Dana-Farber Cancer Institute | Munshi N.C.,Harvard University
Seminars in Oncology | Year: 2013

Multiple myeloma (MM), a heterogeneous plasma cell dyscrasia with a variety of clinical presentations and outcomes, is undergoing a treatment renaissance. While new drug classes have been discovered, a subset of high-risk MM remains relatively refractory to treatment. Current risk stratifications models, such as Durie-Salmon and the International Staging System, estimate disease burden and prognosis. Cytogenetics and gene expression profiles can help further identify more aggressive disease. Additionally, molecular and immunophenotypic assessment of minimal residual disease (MRD) and different imaging studies can identify patients at higher risk for relapse. It is now an opportune time to develop algorithms to combine all of the currently available clinical and genomic information to begin to inform specific therapeutic intervention in individual patients or at least smaller subgroups with similarly behaving disease. © 2013 Published by Elsevier Inc.

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