02586nas a2200289 4500008004100000022001400041245011400055210006900169260001600238520170000254100002601954700002101980700002402001700002302025700002002048700002002068700002002088700001802108700002202126700001902148700002002167700001302187700001902200700001702219700002402236856003602260 2017 eng d a1523-468100aSoluble Inflammatory Markers and Risk of Incident Fractures in Older Adults: The Cardiovascular Health Study.0 aSoluble Inflammatory Markers and Risk of Incident Fractures in O c2017 Oct 043 a

Several in vitro and animal studies have showed that inflammatory markers play a role in bone remodeling and pathogenesis of osteoporosis. Additionally, some human longitudinal studies showed suggestive associations between elevated inflammatory markers and increased risk of nontraumatic fractures. We examined several inflammatory markers and multiple fracture types in a single study of older individuals with extensive follow-up. We assessed the association of four inflammatory markers with the risk of incident hip fractures among 5265 participants of the Cardiovascular Health Study (CHS) and a composite endpoint of incident fractures of the hip, pelvis, humerus, or proximal forearm in 4477 participants. Among CHS participants followed between 1992 and 2009, we observed 480 incident hip fractures during a median follow-up of 11 years. In the composite fracture analysis cohort of 4477 participants, we observed 711 fractures during a median follow-up of 7 years. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for hip fracture associated with doubling of IL-6 were HR 1.15 (95% CI, 1.02 to 1.30) overall and HR 1.17 (95% CI, 1.01 to 1.35) in women. We also observed a positive association between each unit increase in white blood cell (WBC) count and risk of hip fracture: HR 1.04 (95% CI, 1.01 to 1.06) overall and HR 1.06 (95% CI, 0.95 to 1.20) in women. We observed no significant associations between any of the four inflammatory markers and a composite fracture endpoint. Our findings suggest that chronic inflammatory and immune processes may be related to higher rates of incident hip fractures. © 2017 American Society for Bone and Mineral Research.

1 aStojanović, Danijela1 aBůzková, Petra1 aMukamal, Kenneth, J1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aFink, Howard, A1 aCauley, Jane, A1 aWallace, Erin1 aCurtis, Lesley, H1 aHirsch, Calvin1 aBudoff, Matthew1 aLi, Dong1 aYoung, Rebekah1 aJalal, Diana1 aDelaney, Joseph, Ac uhttps://chs-nhlbi.org/node/759203043nas a2200253 4500008004100000022001400041245016700055210006900222260000900291300002100300490000600321520221100327100002402538700001702562700002602579700002102605700002102626700001302647700002402660700002402684700002202708700002302730856003602753 2018 eng d a2050-312100aHospital and clinical care costs associated with atrial fibrillation for Medicare beneficiaries in the Cardiovascular Health Study and the Framingham Heart Study.0 aHospital and clinical care costs associated with atrial fibrilla c2018 a20503121187594440 v63 a

Background: Atrial fibrillation is increasingly prevalent as the US population ages and is associated with significant morbidity and mortality. Care for patients with atrial fibrillation can be costly, US health care costs are comparatively high, and there are few cost estimates available that incorporate detailed measurement of comorbidities and their effects on costs.

Methods and Results: In the Cardiovascular Health Study and the Framingham Heart Study, participants aged 65 years or older with newly diagnosed atrial fibrillation were matched on age and follow-up time to referents free of atrial fibrillation. The total clinical and hospital medical costs paid by Medicare Parts A and B (drug costs from Medicare Part D costs were not included) in the year prior to diagnosis (or matching) were compared with costs in the following year. Estimates were adjusted for other medical conditions and adjusted to 2009 dollars. In the Cardiovascular Health Study, 513 participants were diagnosed with new-onset atrial fibrillation and survived 30 days post-atrial fibrillation diagnosis, and 513 referents (as a control cohort) were identified, with a mean age of 77 years. In the Framingham Heart Study, we identified 336 participants diagnosed with atrial fibrillation, who survived 30 days post-atrial fibrillation diagnosis and matched these participants to 336 referents. We compared these new-onset atrial fibrillation participants with referents, using a difference in difference design to account for both time trends and differences between the two groups. The adjusted incremental cost for participants with atrial fibrillation, compared with referents, was US$18,060 (95% confidence interval: US$14,965-US$21,155) in the Cardiovascular Health Study and US$20,012 (95% confidence interval: US$15,057-US$24,966) in the Framingham Heart Study. The pooled estimate was US$18,601 (95% confidence interval: US$15,981-US$21,234).

Conclusion: Atrial fibrillation was associated with increased costs in the year after diagnosis in two community-based cohorts, even after careful accounting for age, time period, and systematically measured comorbidities.

1 aDelaney, Joseph, Ac1 aYin, Xiaoyan1 aFontes, João, Daniel1 aWallace, Erin, R1 aSkinner, Asheley1 aWang, Na1 aHammill, Bradley, G1 aBenjamin, Emelia, J1 aCurtis, Lesley, H1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/767703449nas a2200517 4500008004100000022001400041245015400055210006900209260001200278300001000290490000800300520194800308653002002256653003102276653003102307653001402338653001102352653002202363653001102385653001402396653001702410653001802427653002002445653002602465653000902491653001402500653001102514653002502525100002602550700002102576700001902597700002302616700002402639700002202663700002002685700001702705700001702722700002102739700001702760700002502777700002702802700002202829700002002851700002402871856003602895 2022 eng d a1879-148400aMonocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study.0 aMonocyte subsets T cell activation profiles and stroke in men an c2022 06 a18-250 v3513 a

BACKGROUND AND AIMS: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke.

METHODS: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models.

RESULTS: We observed associations of intermediate monocytes, early-activated CD4 T cells, and both CD4 and CD8 T cells producing interleukin-4 after cytokine stimulation (T and T, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women.

CONCLUSIONS: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.

10aAtherosclerosis10aCD4-Positive T-Lymphocytes10aCD8-Positive T-Lymphocytes10aCytokines10aFemale10aFollow-Up Studies10aHumans10aIncidence10aInflammation10aInterleukin-410aIschemic Stroke10aLymphocyte Activation10aMale10aMonocytes10aStroke10aT-Lymphocyte Subsets1 aFeinstein, Matthew, J1 aBůzková, Petra1 aOlson, Nels, C1 aDoyle, Margaret, F1 aSitlani, Colleen, M1 aFohner, Alison, E1 aHuber, Sally, A1 aFloyd, James1 aSinha, Arjun1 aThorp, Edward, B1 aLanday, Alan1 aFreiberg, Matthew, S1 aLongstreth, William, T1 aTracy, Russell, P1 aPsaty, Bruce, M1 aDelaney, Joseph, Ac uhttps://chs-nhlbi.org/node/9090