03143nas a2200457 4500008004100000022001400041245011900055210006900174260001300243300001200256490000700268520183100275653001602106653000902122653002202131653001002153653001502163653002802178653001902206653001902225653003502244653001102279653002502290653001102315653002502326653000902351653003002360653003202390653002002422653003002442653001602472653002202488653001802510100002102528700002202549700001802571700002002589700002002609700002002629856003602649 2009 eng d a1758-535X00aTrajectories of dehydroepiandrosterone sulfate predict mortality in older adults: the cardiovascular health study.0 aTrajectories of dehydroepiandrosterone sulfate predict mortality c2009 Dec a1268-740 v643 a

BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) has been proposed as an antiaging hormone, but its importance is unclear. Assessment of an individual's ability to maintain a DHEAS set point, through examination of multiple DHEAS levels over time, may provide insight into biologic aging.

METHODS: Using Cox proportional hazard models, we examined the relationship between DHEAS trajectory patterns and all-cause death in 950 individuals aged >or=65 years who were enrolled in the Cardiovascular Health Study and had DHEAS levels measured at three to six time points.

RESULTS: Overall, there was a slight decline in DHEAS levels over time (-0.013 microg/mL/y). Three trajectory components were examined: slope, variability, and baseline DHEAS. When examined individually, a steep decline or extreme variability in DHEAS levels was associated with higher mortality (p < .001 for each), whereas baseline DHEAS level was not. In adjusted models including all three components, steep decline (hazard ratio [HR] 1.75, confidence interval [CI] 1.32-2.33) and extreme variability (HR 1.89, CI 1.47-2.43) remained significant predictors of mortality, whereas baseline DHEAS level remained unpredictive of mortality (HR 0.97 per standard deviation, CI 0.88-1.07). The effect of trajectory pattern was more pronounced in men than in women. Individuals with both a steep decline and extreme variability in DHEAS levels had a significantly higher death rate than those with neither pattern (141 vs 48 deaths per 1,000 person-years, p < .001).

CONCLUSIONS: Our data show significant heterogeneity in the individual trajectories of DHEAS levels and suggest that these trajectories provide important biologic information about the rate of aging, whereas the DHEAS level itself does not.

10aAge Factors10aAged10aAged, 80 and over10aAging10aBiomarkers10aCardiovascular Diseases10aCause of Death10aCohort Studies10aDehydroepiandrosterone Sulfate10aFemale10aGeriatric Assessment10aHumans10aLongitudinal Studies10aMale10aPredictive Value of Tests10aProportional Hazards Models10aRisk Assessment10aSeverity of Illness Index10aSex Factors10aSurvival Analysis10aUnited States1 aCappola, Anne, R1 aO'Meara, Ellen, S1 aGuo, Wensheng1 aBartz, Traci, M1 aFried, Linda, P1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/112302424nas a2200217 4500008004100000022001400041245009400055210006900149260001600218520174800234100002201982700001802004700002202022700002202044700002302066700002002089700002002109700002002129700002102149856003602170 2017 eng d a1758-535X00aTrajectories of IGF-I Predict Mortality in Older Adults: The Cardiovascular Health Study.0 aTrajectories of IGFI Predict Mortality in Older Adults The Cardi c2017 Jul 233 a

Background: Disruption of insulin-like growth factor-I (IGF-I) increases health and life span in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint.

Methods: Participants were 945 U.S. community-dwelling individuals aged ≥65 years enrolled in the Cardiovascular Health Study with IGF-I levels at 3-6 timepoints. We examined the association of baseline IGF-I level, trajectory slope, and variability around the trajectory with mortality.

Results: There were 633 deaths over median 11.3 years of follow-up. Lower IGF-I levels, declining or increasing slope, and increasing variability were each individually associated with higher mortality (all p < .001). In an adjusted model including all three trajectory parameters, baseline IGF-I levels <70 ng/mL (hazard ratio [HR] 1.58, 95% CI 1.28-1.96 relative to IGF-I levels of 170 ng/mL), steep declines and steep increases in trajectory slope (HR 2.22, 1.30-3.80 for a 15% decline; HR 1.40, 1.07-1.84 for a 10% decline; HR 1.80, 1.12-2.89 for a 15% increase; HR 1.31, 1.00-1.72 for a 10% increase, each vs no change), and variability ≥10% (HR 1.59, 1.09-2.32 for ≥ 30%; HR 1.36, 1.06-1.75 for 20%; and HR 1.17, 1.03-1.32 for 10% variability, each vs 0%) in IGF-I levels were independently associated with mortality.

Conclusions: In contrast to data from animal models, low IGF-I levels are associated with higher mortality in older humans. Irrespective of the actual IGF-I level, older individuals with stability of IGF-I levels have lower mortality than those whose IGF-I levels fluctuate over time.

1 aSanders, Jason, L1 aGuo, Wensheng1 aO'Meara, Ellen, S1 aKaplan, Robert, C1 aPollak, Michael, N1 aBartz, Traci, M1 aNewman, Anne, B1 aFried, Linda, P1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/7584