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      Association between adiponectin and heart failure risk in the Physicians' Health Study

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          Abstract

          Limited data are available on the association between adiponectin and incident heart failure. In the current ancillary study to the Physicians' Health Study, we used a prospective nested-case control design to examine whether plasma adiponectin concentration was related to the risk of heart failure. We selected 787 incident heart failure cases and 787 matched controls for the current analysis. Each control was selected using a risk set sampling technique at the time of the occurrence of the index case and matched on year of birth, age at blood collection, and race. Adiponectin was measured using ELISA. Heart failure occurrence was self-reported in annual follow-up questionnaire. Validation of self-reported heart failure in this cohort has been published. The mean age was 58.7 years. In a conditional logistic regression adjusting for age, race, time of blood collection, year of birth, hypertension, atrial fibrillation, smoking, alcohol intake, and exercise, estimates of the relative risk (95% confidence interval) were 1.0 (ref), 0.74 (0.53–1.04), 0.67 (0.48–0.94), 0.70 (0.50–0.99), and 0.92 (0.65–1.30) from the lowest to the highest quintile of adiponectin, respectively, p for quadratic trend 0.004. Additional adjustment for potential mediating factors including diabetes, C-reactive protein, and body mass index led to the attenuation of the estimate of effect [1.0 (ref), 0.81 (0.57–1.15), 0.75 (0.53–1.06), 0.83 (0.58–1.18), and 1.26 (0.87–1.81) across consecutive quintiles of adiponectin]. Our data are consistent with a J-shaped association between total adiponectin and the risk of heart failure among US male physicians.

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          Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.

          Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.
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            Final report on the aspirin component of the ongoing Physicians' Health Study. Steering Committee of the Physicians' Health Study Research Group.

            The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial designed to determine whether low-dose aspirin (325 mg every other day) decreases cardiovascular mortality and whether beta carotene reduces the incidence of cancer. The aspirin component was terminated earlier than scheduled, and the preliminary findings were published. We now present detailed analyses of the cardiovascular component for 22,071 participants, at an average follow-up time of 60.2 months. There was a 44 percent reduction in the risk of myocardial infarction (relative risk, 0.56; 95 percent confidence interval, 0.45 to 0.70; P less than 0.00001) in the aspirin group (254.8 per 100,000 per year as compared with 439.7 in the placebo group). A slightly increased risk of stroke among those taking aspirin was not statistically significant; this trend was observed primarily in the subgroup with hemorrhagic stroke (relative risk, 2.14; 95 percent confidence interval, 0.96 to 4.77; P = 0.06). No reduction in mortality from all cardiovascular causes was associated with aspirin (relative risk, 0.96; 95 percent confidence interval, 0.60 to 1.54). Further analyses showed that the reduction in the risk of myocardial infarction was apparent only among those who were 50 years of age and older. The benefit was present at all levels of cholesterol, but appeared greatest at low levels. The relative risk of ulcer in the aspirin group was 1.22 (169 in the aspirin group as compared with 138 in the placebo group; 95 percent confidence interval, 0.98 to 1.53; P = 0.08), and the relative risk of requiring a blood transfusion was 1.71. This trial of aspirin for the primary prevention of cardiovascular disease demonstrates a conclusive reduction in the risk of myocardial infarction, but the evidence concerning stroke and total cardiovascular deaths remains inconclusive because of the inadequate numbers of physicians with these end points.
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              Heart failure.

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                Author and article information

                Journal
                101264860
                32902
                Obesity (Silver Spring)
                Obesity (Silver Spring)
                Obesity (Silver Spring, Md.)
                1930-7381
                1930-739X
                20 June 2012
                April 2013
                15 October 2013
                : 21
                : 4
                : 831-834
                Affiliations
                [a ]Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
                [b ]the Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC) and Geriatric Research (GRECC), Boston Veterans Affairs Healthcare System, Boston, MA
                [c ]The Department of Laboratory Medicine & Pathology, University of Minnesota
                Author notes
                Correspondence: Luc Djoussé, MD, MPH, ScD, FAHA Division of Aging, Brigham and Women's Hospital 1620 Tremont St, 3 rd floor; Boston MA 02120 Tel. (617) 525-7591, Fax. (617) 525-7739, ldjousse@ 123456rics.bwh.harvard.edu
                Article
                NIHMS384723
                10.1002/oby.20260
                3479315
                23712986
                9c1776f2-667a-4827-9437-7076e99c9f3a
                History
                Funding
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R01 HL092946 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R01 HL034595-07 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R01 HL026490-03 || HL
                Funded by: National Cancer Institute : NCI
                Award ID: R01 CA097193 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: R01 CA040360 || CA
                Funded by: National Cancer Institute : NCI
                Award ID: R01 CA034944-03 || CA
                Categories
                Article

                Medicine
                adiponectin,epidemiology,heart failure,risk factors
                Medicine
                adiponectin, epidemiology, heart failure, risk factors

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