02841nas a2200421 4500008004100000022001400041245010100055210006900156260001700225300001000242490000700252520165700259653000901916653003001925653002801955653001901983653002702002653001102029653003802040653001102078653001702089653001502106653001702121653001102138653002502149653000902174653001202183653003002195653001702225653001202242653001802254100002402272700002402296700002202320700001802342700002402360856003502384 2004 eng d a1076-746000aTraditional and novel risk factors in older adults: cardiovascular risk assessment late in life.0 aTraditional and novel risk factors in older adults cardiovascula c2004 Mar-Apr a69-800 v133 a

As a population-based, longitudinal study of nearly 6000 older American adults, the Cardiovascular Health Study provides an excellent opportunity to assess the roles of traditional and novel cardiovascular risk factors in the development of coronary heart disease. Cardiovascular Health Study investigators have analyzed both traditional risk factors, such as diabetes, hypertension, and smoking, and new risk factors, such as hemostatic factors, inflammatory markers, exposure to infectious agents, and genetic determinants. These analyses have led to several important conclusions. First, older adults without previous cardiovascular events have a tremendous burden of subclinical vascular disease, which may change how physicians view risk factor modification in this age group. Second, some traditional cardiovascular risk factors lose importance as predictors of cardiovascular disease among older adults. Third, even modest elevations in fasting blood glucose or systolic blood pressure-below the levels used to define diabetes or hypertension-may have prognostic implications. Fourth, novel cardiovascular risk factors may add further information about cardiovascular disease risk in older adults. Promising potential candidates identified in the Cardiovascular Health Study include markers of hemostatic activation, fibrinogen, factor VIII coagulant activity, C-reactive protein, and exposure to herpes simplex virus-1 and possibly chlamydia. Future Cardiovascular Health Study investigations will help to clarify which combination of traditional and newer risk factors provides the best estimate of cardiovascular risk for older adults.

10aAged10aBlood Coagulation Factors10aCardiovascular Diseases10aCohort Studies10aDiabetes Complications10aFemale10aGenetic Predisposition to Disease10aHumans10aHypertension10aInfections10aInflammation10aLipids10aLongitudinal Studies10aMale10aObesity10aPredictive Value of Tests10aRisk Factors10aSmoking10aUnited States1 aMukamal, Kenneth, J1 aKronmal, Richard, A1 aTracy, Russell, P1 aCushman, Mary1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/77202937nas a2200349 4500008004100000022001400041245009500055210006900150260001300219300001100232490000700243520196600250653001602216653000902232653002202241653001102263653001102274653000902285653001702294100002002311700002102331700002002352700001902372700001802391700002102409700002402430700002202454700002702476700002402503700002402527856003602551 2012 eng d a1935-554800aTotal and high-molecular-weight adiponectin and risk of incident diabetes in older people.0 aTotal and highmolecularweight adiponectin and risk of incident d c2012 Feb a415-230 v353 a

OBJECTIVE: To delineate the associations of total adiponectin, high-molecular-weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in older adults.

RESEARCH DESIGN AND METHODS: Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals.

RESULTS: Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMW adiponectin and new-onset diabetes were not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39-0.63]) and HMW adiponectin (0.42 [0.32-0.56]) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables.

CONCLUSIONS: In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation.

10aAdiponectin10aAged10aDiabetes Mellitus10aFemale10aHumans10aMale10aRisk Factors1 aKizer, Jorge, R1 aArnold, Alice, M1 aBenkeser, David1 aIx, Joachim, H1 aDjoussé, Luc1 aZieman, Susan, J1 aBarzilay, Joshua, I1 aTracy, Russell, P1 aMantzoros, Christos, S1 aSiscovick, David, S1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/135603526nas a2200457 4500008004100000022001400041245012000055210006900175260001300244300001100257490000700268520223800275653001602513653001002529653000902539653002202548653001902570653002802589653002502617653001902642653002102661653001102682653001102693653000902704653002102713653003002734653001702764653001102781100002002792700002002812700002102832700001802853700002102871700002402892700002202916700002702938700002402965700002402989700001903013856003603032 2013 eng d a1945-719700aTotal and high-molecular-weight adiponectin and risk of coronary heart disease and ischemic stroke in older adults.0 aTotal and highmolecularweight adiponectin and risk of coronary h c2013 Jan a255-630 v983 a

CONTEXT: Adiponectin is atheroprotective in the laboratory, but prospective studies have shown opposite associations with cardiovascular disease (CVD) in healthy middle-aged populations (protective) and older cohorts (adverse). Whether this relates to different proportions of high-molecular-weight (HMW) adiponectin is unknown.

OBJECTIVE: The aim of the study was to test the hypothesis that total adiponectin is directly associated, but HMW adiponectin is inversely related, with CVD in older adults.

DESIGN, SETTING, AND PARTICIPANTS: We evaluated 3290 participants free of prevalent CVD in a longitudinal cohort study of U.S. adults aged 65 yr and older.

MAIN OUTCOME MEASURES: We measured incident CVD (n = 1291), comprising coronary heart disease and ischemic stroke.

RESULTS: Total and HMW adiponectin were tightly correlated (r = 0.94). Cubic splines adjusted for potential confounders revealed that the associations of total and HMW adiponectin with CVD were U-shaped, with inflection points of 20 and 10 mg/liter, respectively. After controlling for potential confounding, levels of total and HMW adiponectin below these cutpoints tended to be inversely associated with incident CVD, driven by their significant or near-significant relations with coronary heart disease [hazard ratio (HR), 0.85 per sd increase; 95% confidence interval (CI), 0.75-96; and HR, 0.87; 95% CI, 0.75-1.01, respectively]. These associations were abrogated by additional inclusion of putative metabolic intermediates. Above these cutpoints, however, both total and HMW adiponectin were significantly directly associated with CVD after adjustment for confounders and, particularly, mediators (HR, 1.20 per sd increase; 95% CI, 1.06-1.35; and HR, 1.12; 95% CI, 1.02-1.24, respectively).

CONCLUSION: In community-living elders, total and HMW adiponectin showed similar U-shaped relationships with CVD. The inverse relation in the lower range, but not the direct association at the higher end, disappeared after inclusion of putative intermediates, suggesting that high levels may reflect adverse processes separate from adiponectin's beneficial glycometabolic properties.

10aAdiponectin10aAdult10aAged10aAged, 80 and over10aBrain Ischemia10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aCoronary Disease10aFemale10aHumans10aMale10aMolecular Weight10aResidence Characteristics10aRisk Factors10aStroke1 aKizer, Jorge, R1 aBenkeser, David1 aArnold, Alice, M1 aDjoussé, Luc1 aZieman, Susan, J1 aMukamal, Kenneth, J1 aTracy, Russell, P1 aMantzoros, Christos, S1 aSiscovick, David, S1 aGottdiener, John, S1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/613902662nas a2200229 4500008004100000022001400041245014000055210006900195260001600264300001500280520190800295100002402203700001902227700001802246700001902264700002002283700002402303700002102327700002402348700002402372856003602396 2016 eng d a1945-719700aTestosterone, Dihydrotestosterone, Sex Hormone Binding Globulin and Incident Diabetes among Older Men: the Cardiovascular Health Study.0 aTestosterone Dihydrotestosterone Sex Hormone Binding Globulin an c2016 Oct 12 ajc201626233 a

CONTEXT: Although sex hormone binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, or older adults, whose glycemic pathophysiology differs from younger adults.

OBJECTIVE: To determine the associations of SHBG, T, and DHT with insulin resistance and incident diabetes in older adult men.

DESIGN: In a prospective cohort study, we evaluated baseline levels of SHBG, T, and DHT using liquid chromatography-tandem mass spectrometry among 852 men in the Cardiovascular Health Study free of diabetes and cardiovascular disease in 1994.

MAIN OUTCOME: Insulin resistance estimated by HOMA-IR and insulin sensitivity estimated by the Gutt index in 1996, and incident diabetes (n=112) ascertained over a mean follow-up of 9.8 years.

RESULTS: In linear regression models adjusted for demographics, alcohol consumption, current smoking, body-mass index, and other androgens, SHBG (HOMA-IR 0.30 units lower per doubling; 95% confidence interval [CI], 0.08-0.52; p=0.01) and total DHT (HOMA-IR 0.18 units lower per doubling; 95% CI 0.06-0.30; p=0.01), but not free T (p=0.33) were inversely associated with insulin resistance. In corresponding Cox proportional hazards models, total DHT was again inversely associated with risk of diabetes (adjusted hazard ratio per doubling 0.69; 95% CI, 0.52-0.92; p=0.01), but SHBG (hazard ratio 1.09; 95% CI, 0.74-1.59; p=0.66) and free T (hazard ratio 1.15; 95% CI, 0.92-1.43; p=0.23) were not.

CONCLUSIONS: Among older men, higher levels of DHT are inversely associated with insulin resistance and risk of diabetes over the ensuing 10 years, while levels of T are not. Future studies are still needed to clarify the role of SHBG in risk of diabetes in this population.

1 aJoyce, Katherine, E1 aBiggs, Mary, L1 aDjoussé, Luc1 aIx, Joachim, H1 aKizer, Jorge, R1 aSiscovick, David, S1 aShores, Molly, M1 aMatsumoto, Alvin, M1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/7249