02530nas a2200229 4500008004100000022001400041245007700055210006900132260001300201300001200214490000700226520185800233100002402091700002102115700002302136700002002159700002102179700002402200700002002224700002002244856003602264 2020 eng d a1532-841400aSoluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults.0 aSoluble CD14 and Risk of Heart Failure and Its Subtypes in Older c2020 May a410-4190 v263 a
BACKGROUND: CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults.
METHODS AND RESULTS: We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49).
CONCLUSIONS: Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications.
1 aAl-Kindi, Sadeer, G1 aBůzková, Petra1 aShitole, Sanyog, G1 aReiner, Alex, P1 aGarg, Parveen, K1 aGottdiener, John, S1 aPsaty, Bruce, M1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/837602844nas a2200337 4500008004100000022001400041245017600055210006900231260001500300300001400315490000700329520178800336653000902124653002902133653001802162653002202180653001202202653001502214653001102229653002902240653002302269100002402292700002102316700001902337700002202356700002002378700002302398700002502421700002402446856003602470 2022 eng d a1935-554800aThe Association of Measures of Cardiovascular Autonomic Function, Heart Rate, and Orthostatic Hypotension With Incident Glucose Disorders: The Cardiovascular Health Study.0 aAssociation of Measures of Cardiovascular Autonomic Function Hea c2022 10 01 a2376-23820 v453 aOBJECTIVE: The autonomic nervous system (ANS) innervates pancreatic endocrine cells, muscle, and liver, all of which participate in glucose metabolism. We tested whether measures of cardiovascular ANS function are independently associated with incident diabetes and annual change in fasting glucose (FG) levels as well as with insulin secretion and insulin sensitivity in older adults without diabetes.
RESEARCH DESIGN AND METHODS: Heart rate (HR) and measures of HR variability (HRV) were derived from 24-h electrocardiographic monitoring. Blood pressure, seated and standing, was measured. Cox proportional hazards models and linear mixed models were used to analyze the associations between HRV, HR, and orthostatic hypotension (SBP >20 mmHg decline) and incident diabetes or longitudinal FG change.
RESULTS: The mean annual unadjusted FG change was 1 mg/dL. Higher detrended fluctuation analyses (DFA) values, averaged over 4-11 (DFA1) or 12-20 beats (DFA2)-reflecting greater versus less organization of beat-to-beat intervals-were associated with less FG increase over time (per 1-SD increment: DFA1: -0.49 mg/dL/year [-0.96, -0.03]; DFA2: -0.55 mg/dL/year [-1.02, -0.09]). In mutually adjusted analyses, higher SD of the N-N interval (SDNN) was associated with less FG increase over time (per 1-SD increment: SDNN: -0.62 mg/dL/year [-1.22, -0.03]). Higher values of DFA1, DFA2, and SDNN were each associated with greater insulin secretion and insulin sensitivity but not with incident diabetes. We observed no association of HR or orthostatic hypotension with diabetes or FG change.
CONCLUSIONS: Specific measures of cardiac autonomic function are prospectively related to FG level changes and insulin secretion and action.
10aAged10aAutonomic Nervous System10aBlood Glucose10aDiabetes Mellitus10aGlucose10aHeart Rate10aHumans10aHypotension, Orthostatic10aInsulin Resistance1 aBarzilay, Joshua, I1 aTressel, William1 aBiggs, Mary, L1 aStein, Phyllis, K1 aKizer, Jorge, R1 aShitole, Sanyog, G1 aBene-Alhasan, Yakubu1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/915502666nas a2200385 4500008004100000022001400041245009400055210006900149260001600218300001400234490000800248520159500256653000901851653001801860653003001878653001201908653003101920653001101951653001201962653001101974653001201985653002301997653000902020653002402029100002302053700001902076700001902095700002202114700002202136700002402158700001802182700002402200700002002224856003602244 2022 eng d a1476-625600aFasting and Postload Nonesterified Fatty Acids and Glucose Dysregulation in Older Adults.0 aFasting and Postload Nonesterified Fatty Acids and Glucose Dysre c2022 Jun 27 a1235-12470 v1913 aTo evaluate the association of nonesterified fatty acids (NEFA) with dysglycemia in older adults, NEFA levels were measured among participants in the Cardiovascular Health Study (United States; enrolled 1989-1993). Associations with insulin sensitivity and pancreatic β-cell function, and with incident type 2 diabetes mellitus (DM), were examined. The sample comprised 2,144 participants (aged 77.9 (standard deviation, 4.5) years). Participant data from the Cardiovascular Health Study visit in 1996-1997 was used with prospective follow-up through 2010. Fasting and postload NEFA showed significant associations with lower insulin sensitivity and pancreatic β-cell function, individually and on concurrent adjustment. Over median follow-up of 9.7 years, 236 cases of DM occurred. Postload NEFA were associated with risk of DM (per standard deviation, hazard ratio = 1.18, 95% confidence interval: 1.08, 1.29), but fasting NEFA were not (hazard ratio = 1.12, 95% confidence interval: 0.97, 1.29). The association for postload NEFA persisted after adjustment for putative intermediates, and after adjustment for fasting NEFA. Sex and body mass index modified these associations, which were stronger for fasting NEFA with DM in men but were accentuated for postload NEFA in women and among leaner individuals. Fasting and postload NEFA were related to lower insulin sensitivity and pancreatic β-cell function, but only postload NEFA were associated with increased DM. Additional study into NEFA metabolism could uncover novel potential targets for diabetes prevention in elders.
10aAged10aBlood Glucose10aDiabetes Mellitus, Type 210aFasting10aFatty Acids, Nonesterified10aFemale10aGlucose10aHumans10aInsulin10aInsulin Resistance10aMale10aProspective Studies1 aShitole, Sanyog, G1 aBiggs, Mary, L1 aIx, Joachim, H1 aFretts, Amanda, M1 aTracy, Russell, P1 aSiscovick, David, S1 aDjoussé, Luc1 aMukamal, Kenneth, J1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/9295