@article {940, title = {Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke.}, journal = {J Clin Endocrinol Metab}, volume = {92}, year = {2007}, month = {2007 Apr}, pages = {1319-25}, abstract = {

CONTEXT: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.

OBJECTIVE: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke.

DESIGN AND PARTICIPANTS: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study.

MAIN OUTCOME MEASURES: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study.

RESULTS: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95\% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease.

CONCLUSION: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.

}, keywords = {Aged, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Coronary Disease, Female, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Multivariate Analysis, Risk Factors, Stroke}, issn = {0021-972X}, doi = {10.1210/jc.2006-1631}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis H and Strickler, Howard D and Rohan, Tom E and Cappola, Anne R and Xue, XiaoNan and Psaty, Bruce M} } @article {1035, title = {High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly.}, journal = {Am Heart J}, volume = {155}, year = {2008}, month = {2008 Jun}, pages = {1006-12}, abstract = {

BACKGROUND: Low levels of insulinlike growth factor 1 (IGF-I) may influence the development of age-related cardiovascular diseases including congestive heart failure (CHF). Insulinlike growth factor binding protein 1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in patients with CHF and has been associated prospectively with increased mortality among older adults and survivors of myocardial infarction. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study.

METHODS: From among 5,888 adults 65 years old and older in the Cardiovascular Health Study, we studied 566 incident CHF cases and 1,072 comparison subjects after exclusion of underweight individuals (body mass index <18.5 kg/m(2)) and insulin users. Hazard ratios (HRs) with 95\% CIs for CHF were estimated after adjustment for age, race, sex, hypertension, systolic blood pressure, lipid levels, left ventricular hypertrophy, coronary disease, C-reactive protein, health status, diabetes, and body mass index.

RESULTS: High baseline IGFBP-1 level was a significant predictor of CHF, independent of established CHF risk factors and inflammation markers. The HR per SD of IGFBP-1 was 1.22 (95\% CI 1.07-1.39, P < .01). Relative to the lowest IGFBP-1 tertile, the HR was 1.29 (95\% CI 0.96-1.74, P = .09) for the second IGFBP-1 tertile and 1.47 (95\% CI 1.06-2.04; P = .02) for the highest IGFBP-1 tertile (tertile cut points 19.5 and 35.8 ng/mL). Total IGF-I, IGFBP-3, or insulin levels had no association with CHF after adjustment for CHF risk factors.

CONCLUSIONS: High circulating IGFBP-1 level may be a CHF risk factor among older adults.

}, keywords = {Aged, Aged, 80 and over, Female, Heart Failure, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Predictive Value of Tests, Prospective Studies, Risk Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2007.12.031}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis and Strickler, Howard D and Rohan, Thomas E and Cappola, Anne R and Xue, XiaoNan and Psaty, Bruce M} } @article {1374, title = {Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study.}, journal = {J Clin Endocrinol Metab}, volume = {97}, year = {2012}, month = {2012 Jun}, pages = {1970-6}, abstract = {

BACKGROUND: The association between changes in IGF-I and IGF binding protein (IGFBP) levels and mortality in older adults is unknown.

STUDY DESIGN: Participants were 997 persons 77 to 100 yr old enrolled in the Cardiovascular Health Study All Stars Study. Plasma levels of IGF-I, IGFBP-1, and IGFBP-3 were assessed at two study examinations (1996-1997 and 2005-2006). Mortality was assessed between 2006 and 2010.

RESULTS: Cumulative mortality (CM) was similar among individuals who had at least 10\% decreases over time in IGF-I levels (CM = 29.6\%), individuals who had at least 10\% increases over time in IGF-I levels (CM = 24.7\%), and individuals who had IGF-I levels remaining within {\textpm}10\% over time (CM = 23.5\%). Adjusted for age, sex, race, diabetes, body mass index, creatinine, albumin, and C-reactive protein, decreasing IGF-I level had no significant association with overall cancer mortality or noncancer mortality. Levels of IGFBP-1 increased markedly over time by 38\% (median). Individuals with the largest increases in IGFBP-1 level over time had significantly increased risk of mortality. The adjusted hazard ratio per sd of IGFBP-1 change was 1.40 for overall cancer mortality (95\% confidence interval = 1.10, 1.77; P = 0.01) and 1.14 for noncancer mortality (95\% confidence interval = 1.02, 1.27; P = 0.02). Changes in IGFBP-3 levels were not significantly associated with mortality.

CONCLUSION: Among older adults, decreasing IGF-I level over time does not predict subsequent all-cause mortality, whereas increasing IGFBP-1 predicts increased risk of mortality.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Cardiovascular Diseases, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Longitudinal Studies, Male, Mortality, Predictive Value of Tests, Risk Factors}, issn = {1945-7197}, doi = {10.1210/jc.2011-2967}, author = {Kaplan, Robert C and B{\r u}zkov{\'a}, Petra and Cappola, Anne R and Strickler, Howard D and McGinn, Aileen P and Mercer, Laina D and Arnold, Alice M and Pollak, Michael N and Newman, Anne B} } @article {6000, title = {Do changes in circulating biomarkers track with each other and with functional changes in older adults?}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Feb}, pages = {174-81}, abstract = {

BACKGROUND: It is unclear if changes in proposed circulating biomarkers of aging are strongly correlated to each other or functional change. We tested if biomarker changes track with each other and with functional measures over 9 years in older adults.

METHODS: Dehydroepiandrosterone sulfate (DHEAS), adiponectin, insulin-like growth factor 1 (IGF-1), IGF binding proteins 1 (IGFBP-1) and 3 (IGFBP-3), interleukin-6 (IL-6), cholesterol, and function (gait speed, grip strength, Modified Mini Mental Status Exam [3MSE] and Digit Symbol Substitution Test [DSST] scores) were measured in 1996-1997 and 2005-2006 in the Cardiovascular Health Study All Stars study (N = 901, mean [standard deviation, SD] age 85.3 [3.6] years in 2005-2006). Adjusted Pearson correlations illustrated if biomarkers tracked together. Multivariable linear regression demonstrated if biomarker changes tracked with functional changes.

RESULTS: Correlations among biomarker changes were mostly <0.2. In models with each biomarker entered separately, a 1-SD increase biomarker change was associated with change in function as follows: grip strength (DHEAS β = 0.61kg, p = .001; IL-6 β = -0.46kg, p = .012; cholesterol men β = 0.79kg, p = .016); gait speed (DHEAS β = 0.02 meters per second, p = .039; IL-6 β = -0.018 meters per second, p = .049); and DSST score (DHEAS women β = 1.46, p = .004; IL-6 β = -0.83, p = .027). When biomarkers were entered in the same model, significant associations remaining were as follows: grip strength (DHEAS β = 0.54kg, p = .005; IL-6 β = -0.43kg, p = .022); 3MSE score (IGF-1 β = 0.96, p = .04; IGFBP-3 β = -1.07, p = .024); and DSST score (DHEAS women β = 1.27, p = .012; IL-6 β = -0.80, p = .04).

CONCLUSION: Changes in biomarkers were poorly correlated, supporting a model of stochastic, independent change across systems. DHEAS and IL-6 tracked most closely with function, illustrating that changes in inflammation and sex steroids may play dominant roles in changes of these functional outcomes.

}, keywords = {Adiponectin, Aged, Aged, 80 and over, Aging, Biomarkers, Cholesterol, Cognition, Cohort Studies, Dehydroepiandrosterone Sulfate, Female, Gait, Hand Strength, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Interleukin-6, Male, Neuropsychological Tests, Psychomotor Performance, Time Factors}, issn = {1758-535X}, doi = {10.1093/gerona/glt088}, author = {Sanders, Jason L and Ding, Victoria and Arnold, Alice M and Kaplan, Robert C and Cappola, Anne R and Kizer, Jorge R and Boudreau, Robert M and Cushman, Mary and Newman, Anne B} }