02821nas a2200433 4500008004100000022001400041245008000055210006900135260001300204300001000217490000600227520161000233653000901843653002201852653001501874653002701889653003101916653001101947653002201958653001101980653001401991653000902005653003202014653002402046653002602070653001702096100001802113700001902131700001902150700002002169700002402189700002202213700002102235700002502256700002202281700002402303700002402327856003602351 2012 eng d a1941-308400aNonesterified fatty acids and risk of sudden cardiac death in older adults.0 aNonesterified fatty acids and risk of sudden cardiac death in ol c2012 Apr a273-80 v53 a

BACKGROUND: Although nonesterified fatty acids (NEFA) have been positively associated with coronary heart disease risk factors, limited and inconsistent data are available on the relation between NEFA and sudden cardiac death.

METHODS AND RESULTS: Using a prospective design, we studied 4657 older men and women (mean age, 75 years) from the Cardiovascular Health Study (1992-2006) to evaluate the association between plasma NEFA and the risk of sudden cardiac death in older adults. Plasma concentrations of NEFA were measured using established enzymatic methods, and sudden death was adjudicated using medical records, death certificates, proxy interview, and autopsy reports. We used Cox proportional hazard models to estimate multivariable-adjusted relative risks. During a median follow-up of 10.0 years, 221 new cases of sudden cardiac death occurred. In a multivariable model adjusting for age, sex, race, clinic site, alcohol intake, smoking, prevalent coronary heart disease and heart failure, and self-reported health status, relative risks (95% confidence interval) for sudden cardiac death were 1.0 (ref), 1.15 (0.81-1.64), 1.06 (0.72-1.55), and 0.91 (0.60-1.38) across consecutive quartiles of NEFA concentration. In secondary analyses restricted to the first 5 years of follow-up, we also did not observe a statistically significant association between plasma NEFA and sudden cardiac death.

CONCLUSIONS: Our data do not provide evidence for an association between plasma NEFA measured late in life and the risk of sudden cardiac death in older adults.

10aAged10aAged, 80 and over10aBiomarkers10aDeath, Sudden, Cardiac10aFatty Acids, Nonesterified10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aProportional Hazards Models10aProspective Studies10aRetrospective Studies10aRisk Factors1 aDjoussé, Luc1 aBiggs, Mary, L1 aIx, Joachim, H1 aKizer, Jorge, R1 aLemaitre, Rozenn, N1 aSotoodehnia, Nona1 aZieman, Susan, J1 aMozaffarian, Dariush1 aTracy, Russell, P1 aMukamal, Kenneth, J1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/136102520nas a2200181 4500008004100000022001400041245010500055210006900160260001600229520193100245100002402176700002102200700001802221700001902239700002002258700002402278856003602302 2020 eng d a1758-535X00aNon-Esterified Fatty Acids and Hospitalizations among Older Adults: The Cardiovascular Health Study.0 aNonEsterified Fatty Acids and Hospitalizations among Older Adult c2020 Sep 103 a

BACKGROUND: We sought to determine associations between total serum concentrations of non-esterified fatty acids (NEFAs) and incident total and cause-specific hospitalizations in a community-living cohort of elders.

METHODS: We included 4715 participants in the Cardiovascular Health Study who had fasting total serum NEFA measured at the 1992/93 clinic visit and were followed for a median of 12 years. We identified all inpatient admissions requiring at least an overnight hospitalization and used primary diagnostic codes to categorize cause-specific hospitalizations. We used Cox proportional hazards regression models to determine associations with time-to-first hospitalization and Poisson regression for the rate ratios (RR) of hospitalizations and days hospitalized.

RESULTS: We identified 21339 hospitalizations during follow-up. In fully adjusted models, higher total NEFAs were significantly associated with higher risk of incident hospitalization (Hazard Ratio (HR) per SD [0.2 mEq/L]=1.07, 95%CI=1.03-1.10, P&0.001), number of hospitalizations (RR per SD=1.04, 95%CI=1.01-1.07, P=0.01), and total number of days hospitalized (RR per SD=1.06, 95%CI=1.01-1.10, P=0.01). Among hospitalization subtypes, higher NEFA was associated with higher likelihood of mental, neurologic, respiratory, and musculoskeletal causes of hospitalization. Among specific causes of hospitalization, higher NEFA was associated with diabetes, pneumonia, and gastrointestinal hemorrhage.

CONCLUSIONS: Higher fasting total serum NEFAs are associated with a broad array of causes of hospitalization among older adults. While some of these were expected, our results illustrate a possible utility of NEFAs as biomarkers for risk of hospitalization, and total days hospitalized, in older adults. Further research is needed to determine whether interventions based on NEFAs might be feasible.

1 aAhiawodzi, Peter, D1 aBůzková, Petra1 aDjoussé, Luc1 aIx, Joachim, H1 aKizer, Jorge, R1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/847603050nas a2200205 4500008004100000022001400041245013900055210006900194260001600263520237000279100002102649700001802670700001902688700002002707700002202727700001802749700001702767700002402784856003602808 2020 eng d a1532-541500aNon-Esterified Fatty Acids and Risks of Frailty, Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study.0 aNonEsterified Fatty Acids and Risks of Frailty Disability and Mo c2020 Sep 223 a

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.

1 aAhiawodzi, Peter1 aDjoussé, Luc1 aIx, Joachim, H1 aKizer, Jorge, R1 aTracy, Russell, P1 aArnold, Alice1 aNewman, Anne1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/847702690nas a2200205 4500008004100000022001400041245010100055210006900156260001300225300001100238490000600249520206300255100002102318700002802339700001802367700001902385700002002404700002402424856003602448 2020 eng d a2589-936800aNon-esterified fatty acids and telomere length in older adults: The Cardiovascular Health Study.0 aNonesterified fatty acids and telomere length in older adults Th c2020 Dec a1000580 v83 a

Background: Telomeres shorten as organisms age, placing limits on cell proliferation and serving as a marker of biological aging. Non-esterified fatty acids (NEFAs) are a key mediator of age-related metabolic abnormalities. We aimed to determine if NEFAs are associated with telomere length in community-living older adults.

Material and methods: We cross-sectionally studied 1648 participants of the Cardiovascular Health Study (CHS) who underwent concomitant telomere length measurement from a sample of 4715 participants who underwent measurement of circulating total fasting NEFAs in stored specimens from their 1992-3 clinic visit. We used linear regression and inverse probability weighting to model telomere length as a function of NEFAs with adjustment for age, gender, race, clinic, BMI, marital status, smoking status, alcohol intake, diabetes status, years of education, hypertension status, prevalent cardiovascular disease, C-reactive protein, total adiponectin, albumin, fetuin-A, fasting insulin, eGFR, total cholesterol, HDL-cholesterol, triglycerides, and general health status.

Results: Higher NEFAs were significantly associated with shorter telomere length, after adjusting for age, gender, race, and clinic site (β = -0.034; SE = 0.015;  = 0.02). Estimates remained similar in fully adjusted models where each SD of NEFA increment was associated with 0.042 kilobase (kb) pairs shorter telomere length (standard error = 0.016;  = 0.007); for comparison the coefficient for a single year of age in the same model was -0.017. These results were similar in strata of sex, and waist circumference although they tended to be strongest among participants in the youngest tertile of age (β = -0.079; SE = 0.029; P = 0.01).

Conclusions: In this population-based cohort of community-living elders, we observed a significant inverse association between NEFAs and telomere length. If confirmed, NEFAs may represent a promising target for interventions to slow biological aging.

1 aAhiawodzi, Peter1 aFitzpatrick, Annette, L1 aDjoussé, Luc1 aIx, Joachim, H1 aKizer, Jorge, R1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/847802928nas a2200193 4500008004100000022001400041245012200055210006900177260001600246520228800262100002102550700001902571700001902590700002002609700002702629700001802656700002402674856003602698 2021 eng d a1523-683800aNonesterified Fatty Acids and Kidney Function Decline in Older Adults: Findings From the Cardiovascular Health Study.0 aNonesterified Fatty Acids and Kidney Function Decline in Older A c2021 Feb 033 a

RATIONALE & OBJECTIVE: Circulating non-esterified fatty acids (NEFAs) make up a small portion of circulating lipids but are a metabolically important energy source. Excessive circulating NEFAs may contribute to lipotoxicity in many tissues, including the kidneys. We investigated the relationship between total circulating NEFA concentration and kidney outcomes in older, community-dwelling adults.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 4,698 participants ≥65 years of age in the Cardiovascular Health Study who underwent total fasting serum NEFA concentration measurements in 1992-1993.

EXPOSURE: Fasting serum NEFA concentration at one timepoint.

OUTCOMES: Three primary outcomes: estimated glomerular filtration rate (eGFR) decline of >30%; the composite of eGFR decline ≥30% or kidney failure with replacement therapy (KFRT); and change in eGFR. These outcomes were assessed over 4- and 13-year periods.

ANALYTICAL APPROACH: Logistic regression for the dichotomous outcomes and mixed effects models for the continuous outcome, with sequential adjustment for baseline covariates. Inverse probability of attrition weighting was implemented to account for informative attrition during the follow-up periods.

RESULTS: Serum NEFA concentrations were not independently associated with kidney outcomes. In unadjusted and partially adjusted analyses, the highest quartile of serum NEFA concentration (compared to lowest) was associated with a higher risk of ≥30% eGFR decline at 4 years and faster rate of decline of eGFR. No associations were evident after adjustment for comorbidities, lipid levels, insulin sensitivity, medications, and vital signs: odds ratio 1.33 (95%CI 0.83-2.13); estimated glomerular filtration rate change per year, Q4 vs Q1: -0.15 ml/min/1.73m/year (95%CI -0.36 to 0.06).

LIMITATIONS: Single NEFA measurements, no measurements of post-glucose load NEFA concentrations or individual NEFA species, no measurement of baseline urine albumin.

CONCLUSIONS: A single fasting serum NEFA concentration was not independently associated with long-term adverse kidney outcomes in a cohort of older community-living adults.

1 aWalther, Carl, P1 aIx, Joachim, H1 aBiggs, Mary, L1 aKizer, Jorge, R1 aNavaneethan, Sankar, D1 aDjoussé, Luc1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/866802581nas a2200229 4500008004100000022001400041245011900055210006900174260001600243520184500259100002102104700002602125700002302151700001902174700002002193700002202213700001702235700002102252700001802273700002402291856003602315 2023 eng d a1879-148400aNon-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study.0 aNonesterified fatty acids and risk of peripheral artery disease  c2023 Jan 293 a

BACKGROUND AND AIMS: Non-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons.

METHODS: We evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992-1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998-1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI.

RESULTS: Mean age was 74.8 years, 59% were female, and 17% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95%CI = 1.06-2.13, p = 0.02) across extreme tertiles, and 1.14 (95%CI = 0.99-1.31, p = 0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95%CI = 0.69-1.32, p = 0.76) across extreme tertiles, and 1.03 (95%CI = 0.89-1.20, p = 0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up.

CONCLUSIONS: Higher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.

1 aAhiawodzi, Peter1 aSolaru, Khendi, White1 aChaves, Paulo, H M1 aIx, Joachim, H1 aKizer, Jorge, R1 aTracy, Russell, P1 aNewman, Anne1 aSiscovick, David1 aDjoussé, Luc1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/9284