Peter Ahiawodzi1, Luc Djousse2, Joachim H Ix3, Jorge R Kizer4, Russell P Tracy5, Alice Arnold6, Anne Newman7, Kenneth J Mukamal8. 1. Department of Public Health, Campbell University College of Pharmacy and Health Sciences, Buies Creek, North Carolina, USA. 2. Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. 3. Divisions of Nephrology and Preventive Medicine, University of California, San Diego, San Diego, California, USA. 4. Division of Cardiology, Veterans Affairs Medical Center, University of California, San Francisco, California, USA. 5. Department of Pathology and Biochemistry, University of Vermont College of Medicine, Burlington, Vermont, USA. 6. Department of a Biostatistics, University of Washington, Seattle, Washington, USA. 7. Departments of Epidemiology and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 8. Division of General Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Abstract
BACKGROUND/ OBJECTIVES: Non-esterified fatty acids (NEFAs) play central roles in the relationship between adiposity and glucose metabolism, and they have been implicated in the pathogenesis of cardiovascular disease, but few studies have assessed their effects on complex geriatric syndromes like frailty that cross multiple organ systems. We sought to determine the relationships between NEFAs and incident frailty, disability, and mobility limitation in a population-based cohort of older persons. METHODS: We analyzed 4,710 Cardiovascular Health Study (CHS) participants who underwent measurement of circulating total fasting NEFAs in 1992-1993 and were assessed for frailty in 1996-1997 and for disability and mobility limitation annually. We used ordinal logistic regression to model incident frailty, linear regression to model components of frailty, and Cox regression to model disability and mobility limitation in relation to baseline NEFAs. To ensure proportional hazards, we truncated follow-up at 9 years for disability and 6.5 years for mobility limitation. RESULTS: A total of 42 participants became frail and 510 became pre-frail over a 4-year period, and we documented 1,720 cases of disability and 1,225 cases of mobility limitation during follow-up. NEFAs were positively associated in a dose-dependent manner with higher risks of incident frailty, disability, and mobility limitation. The adjusted odds ratios for frailty were 1.37 (95% confidence interval [CI] = 1.01-1.86; P = .04) across extreme tertiles and 1.17 (95% CI = 1.03-1.33; P = .01) per standard deviation increment. The corresponding hazard ratios for incident disability were 1.14 (95% CI = 1.01-1.30; P = .04) and 1.11 (95% CI = 1.06-1.17; P < .0001); those for incident mobility limitation were 1.23 (95% CI = 1.06-1.43; P = .006) and 1.15 (95% CI = 1.08-1.22; P < .0001). Results were largely consistent among both men and women. Among individual components of frailty, NEFAs were significantly associated with self-reported exhaustion (β = .07; standard error = .03; P = .02). CONCLUSION: Circulating NEFAs are significantly associated with frailty, disability, and mobility limitation among older adults. These results highlight the broad spectrum of adverse health issues associated with NEFA in older adults.
BACKGROUND/ OBJECTIVES: Non-esterified fatty acids (NEFAs) play central roles in the relationship between adiposity and glucose metabolism, and they have been implicated in the pathogenesis of cardiovascular disease, but few studies have assessed their effects on complex geriatric syndromes like frailty that cross multiple organ systems. We sought to determine the relationships between NEFAs and incident frailty, disability, and mobility limitation in a population-based cohort of older persons. METHODS: We analyzed 4,710 Cardiovascular Health Study (CHS) participants who underwent measurement of circulating total fasting NEFAs in 1992-1993 and were assessed for frailty in 1996-1997 and for disability and mobility limitation annually. We used ordinal logistic regression to model incident frailty, linear regression to model components of frailty, and Cox regression to model disability and mobility limitation in relation to baseline NEFAs. To ensure proportional hazards, we truncated follow-up at 9 years for disability and 6.5 years for mobility limitation. RESULTS: A total of 42 participants became frail and 510 became pre-frail over a 4-year period, and we documented 1,720 cases of disability and 1,225 cases of mobility limitation during follow-up. NEFAs were positively associated in a dose-dependent manner with higher risks of incident frailty, disability, and mobility limitation. The adjusted odds ratios for frailty were 1.37 (95% confidence interval [CI] = 1.01-1.86; P = .04) across extreme tertiles and 1.17 (95% CI = 1.03-1.33; P = .01) per standard deviation increment. The corresponding hazard ratios for incident disability were 1.14 (95% CI = 1.01-1.30; P = .04) and 1.11 (95% CI = 1.06-1.17; P < .0001); those for incident mobility limitation were 1.23 (95% CI = 1.06-1.43; P = .006) and 1.15 (95% CI = 1.08-1.22; P < .0001). Results were largely consistent among both men and women. Among individual components of frailty, NEFAs were significantly associated with self-reported exhaustion (β = .07; standard error = .03; P = .02). CONCLUSION: Circulating NEFAs are significantly associated with frailty, disability, and mobility limitation among older adults. These results highlight the broad spectrum of adverse health issues associated with NEFA in older adults.
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