03386nas a2200505 4500008004100000022001400041245011100055210006900166260001300235300001200248490000700260520193600267653000902203653002202212653001502234653002802249653001902277653002802296653002402324653001102348653002202359653001102381653001402392653002502406653000902431653001602440653002402456653003302480653003202513653002402545653001702569653001102586653002202597653001802619100002102637700002402658700001902682700001902701700002702720700002302747700002502770700002402795700002502819856003602844 2012 eng d a1938-320700aNovel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study.0 aNovel circulating fatty acid patterns and risk of cardiovascular c2012 Dec a1252-610 v963 a

BACKGROUND: Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns related to cardiovascular disease (CVD) risk.

OBJECTIVES: We aimed to derive FA patterns from circulating FAs, relate the patterns to CVD incidence, and extend the derived patterns to atherosclerosis progression in another independent cohort.

DESIGN: We used principal component analysis (PCA) to derive FA patterns from 38 plasma phospholipid FAs in 2972 older adults in the Cardiovascular Health Study (CHS). Identified patterns were evaluated for prospective associations with 14-y incidence of CVD [ischemic heart disease (IHD) or stroke]. In another independent cohort of postmenopausal women with IHD, we evaluated associations of the CHS-derived patterns with 3.2-y progression of angiographically defined coronary atherosclerosis.

RESULTS: Three distinct patterns were identified, characterized by higher proportions of trans FAs, de novo lipogenesis (DNL) FAs, and long-chain MUFAs (LCMUFAs). During 32,265 person-years, 780 incident CVD events occurred. The trans FA pattern was associated with higher CVD risk (multivariable-adjusted HR for the highest compared with the lowest quintiles = 1.58; 95% CI: 1.17, 2.12; P-trend = 0.006), primarily attributable to higher risk of stroke (HR: 2.46; 95% CI: 1.54, 3.92; P-trend = 0.005). The DNL and LCMUFA patterns were not associated with CVD incidence or with IHD or stroke (P-trend > 0.11 each). In the second cohort, the trans FA pattern, but not the other 2 patterns, was positively associated with progression of coronary atherosclerosis (P-trend < 0.05).

CONCLUSIONS: PCA appears to provide informative circulating FA patterns. A pattern driven mainly by trans FA levels related to greater CVD risk in older adults and coronary atherosclerosis progression in women with IHD.

10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aCoronary Artery Disease10aDisease Progression10aFemale10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMale10aMiddle Aged10aMyocardial Ischemia10aPrincipal Component Analysis10aProportional Hazards Models10aProspective Studies10aRisk Factors10aStroke10aTrans Fatty Acids10aUnited States1 aImamura, Fumiaki1 aLemaitre, Rozenn, N1 aKing, Irena, B1 aSong, Xiaoling1 aLichtenstein, Alice, H1 aMatthan, Nirupa, R1 aHerrington, David, M1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/141002582nas a2200241 4500008004100000022001400041245017200055210006900227260001600296300001200312490000700324520177900331100001902110700002102129700002302150700001802173700002202191700002002213700002002233700002402253700002702277856003602304 2021 eng d a2047-998000aAssociations of Serum Nonesterified Fatty Acids With Coronary Heart Disease Mortality and Nonfatal Myocardial Infarction: The CHS (Cardiovascular Health Study) Cohort.0 aAssociations of Serum Nonesterified Fatty Acids With Coronary He c2021 Mar 16 ae0191350 v103 a

Background Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n-6 and n-3], and fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. Methods and Results CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996-1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow-up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; =0.0328) and dihomo-γ-linolenic acid (20:3n-6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02-1.76; =0.0351). Elaidic acid (18:1n-7) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01-2.12; =0.0445). No significant associations were observed for NEFA subclass and any outcomes. Conclusions In CHS participants, 2 NEFAs, dihomo-γ-linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.

1 aHuang, Neil, K1 aBůzková, Petra1 aMatthan, Nirupa, R1 aDjoussé, Luc1 aHirsch, Calvin, H1 aKizer, Jorge, R1 aLongstreth, W T1 aMukamal, Kenneth, J1 aLichtenstein, Alice, H uhttps://chs-nhlbi.org/node/870702579nas a2200241 4500008004100000022001400041245008900055210006900144260001600213520182700229100002402056700002102080700002702101700002302128700001902151700002402170700002302194700002202217700002402239700001802263700002002281856003602301 2021 eng d a1468-201X00aIndividual non-esterified fatty acids and incident atrial fibrillation late in life.0 aIndividual nonesterified fatty acids and incident atrial fibrill c2021 Jan 223 a

OBJECTIVE: Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Expansion of fat depots is associated with increased circulating total non-esterified fatty acids (NEFAs), elevated levels of which are associated with incident AF. We undertook comprehensive serum measurement of individual NEFA to identify specific associations with new-onset AF late in life.

METHODS: The present study focused on participants with available serum and free of AF selected from the Cardiovascular Health Study, a community-based longitudinal investigation of older US adults. Thirty-five individual NEFAs were measured by gas chromatography. Cox regression was used to evaluate the association of individual NEFAs with incident AF.

RESULTS: The study sample included 1872 participants (age 77.7±4.4). During median follow-up of 11.3 years, 715 cases of incident AF occurred. After concurrent adjustment of all NEFAs and full adjustment for potential confounders, higher serum concentration of nervonic acid (24:1 n-9), a long-chain monounsaturated fatty acid, was associated with higher risk of AF (HR per SD: 1.18, 95% CI 1.08 to 1.29; p<0.001). Conversely, higher serum concentration of gamma-linolenic acid (GLA) (18:3 n-6), a polyunsaturated n-6 fatty acid, was associated with lower risk of AF (HR per SD: 0.81, 95% CI 0.71 to 0.94; p=0.004). None of the remaining NEFAs was significantly associated with AF.

CONCLUSIONS: Among older adults, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified GLA were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF prevention and early intervention in this segment of the population at highest risk.

1 aPellegrini, Cara, N1 aBůzková, Petra1 aLichtenstein, Alice, H1 aMatthan, Nirupa, R1 aIx, Joachim, H1 aSiscovick, David, S1 aHeckbert, Susan, R1 aTracy, Russell, P1 aMukamal, Kenneth, J1 aDjoussé, Luc1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/866502619nas a2200265 4500008004100000022001400041245009000055210006900145260001600214300000800230520181500238100001802053700001902071700002302090700001902113700002802132700001602160700002402176700002202200700002002222700002702242700002402269700002402293856003602317 2021 eng d a1421-975100aSerum Individual Nonesterified Fatty Acids and Risk of Heart Failure in Older Adults.0 aSerum Individual Nonesterified Fatty Acids and Risk of Heart Fai c2021 Feb 25 a1-83 a

BACKGROUND: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined.

OBJECTIVE: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults.

METHODS: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee.

RESULTS: The mean age was 77.7 ± 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57-0.94]), γ-linolenic acid (GLA) (0.87 [0.75-1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61-0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04-1.63]) and nervonic (24:1n-9) (1.17 [1.06-1.29]) acids with HF.

CONCLUSION: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.

1 aDjoussé, Luc1 aBiggs, Mary, L1 aMatthan, Nirupa, R1 aIx, Joachim, H1 aFitzpatrick, Annette, L1 aKing, Irena1 aLemaitre, Rozenn, N1 aMcKnight, Barbara1 aKizer, Jorge, R1 aLichtenstein, Alice, H1 aMukamal, Kenneth, J1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/870402882nas a2200337 4500008004100000022001400041245006600055210006400121260001500185300001200200490000700212520191900219653003202138653003102170653002502201653002302226653001102249653002402260653001702284653001102301653002202312100001902334700001902353700002302372700001802395700002002413700002402433700002402457700002702481856003602508 2021 eng d a2047-998000aSerum Nonesterified Fatty Acids and Incident Stroke: The CHS.0 aSerum Nonesterified Fatty Acids and Incident Stroke The CHS c2021 11 16 ae0227250 v103 a

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996-1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)-6 polyunsaturated, n-3 polyunsaturated, and fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5-year follow-up period. Total n-3 (hazard ratio [HR], 0.77 [95% CI, 0.61-0.97]) and n-6 (HR, 1.32 [95% CI, 1.01-1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo-γ-linolenic acid (20:3n-6) was associated with higher risk (HR, 1.29 [95% CI, 1.02-1.63]), whereas -7-hexadecenoic acid (16:1n-9) and arachidonic acid (20:4n-6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47-0.97]; HR, 0.81 [95% CI. 0.65-1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n-3 subclass and dihomo-γ-linolenic acid are diet derived and may be potential biomarkers for total stroke risk.

10a8,11,14-Eicosatrienoic Acid10aFatty Acids, Nonesterified10aFatty Acids, Omega-310aHemorrhagic Stroke10aHumans10aProspective Studies10aRisk Factors10aStroke10aTrans Fatty Acids1 aHuang, Neil, K1 aBiggs, Mary, L1 aMatthan, Nirupa, R1 aDjoussé, Luc1 aLongstreth, W T1 aMukamal, Kenneth, J1 aSiscovick, David, S1 aLichtenstein, Alice, H uhttps://chs-nhlbi.org/node/899303103nas a2200421 4500008004100000022001400041245015900055210006900214260001600283490000700299520182900306653000902135653002202144653002002166653001502186653002002201653002702221653003502248653001502283653003302298653003102331653001102362653001102373653001802384653000902402653002402411653001702435653002002452100001902472700002102491700002302512700001802535700002002553700002402573700002102597700002702618856003602645 2021 eng d a2072-664300aSerum Non-Esterified Fatty Acids, Carotid Artery Intima-Media Thickness and Flow-Mediated Dilation in Older Adults: The Cardiovascular Health Study (CHS).0 aSerum NonEsterified Fatty Acids Carotid Artery IntimaMedia Thick c2021 Aug 310 v133 a

Elevated common carotid artery intima-media thickness (carotid IMT) and diminished flow-mediated dilation (FMD) are early subclinical indicators of atherosclerosis. Serum total non-esterified fatty acid (NEFA) concentrations have been positively associated with subclinical atherosclerosis. The relations between individual NEFA, carotid IMT and FMD have as yet to be assessed. We investigated the associations between fasting serum individual NEFA, carotid IMT and FMD among Cardiovascular Health Study (CHS) participants with ( = 255 for carotid IMT, 301 for FMD) or without ( = 1314 for carotid IMT, 1462 for FMD) known atherosclerotic cardiovascular disease (ASCVD). Using archived samples (fasting) collected from 1996-1997 (baseline), 35 individual NEFAs were measured using gas chromatography. Carotid IMT and estimated plaque thickness (mean of maximum internal carotid IMT) were determined in 1998-1999. FMD was measured in 1997-1998. Linear regression adjusted by the Holm-Bonferroni method was used to assess relations between individual NEFA, carotid IMT and FMD. In multivariable adjusted linear regression models per SD increment, the non-esterified fatty acid conjugated linoleic acid (-18:2 CLA) was positively associated with carotid IMT [β (95% CI): 44.8 (19.2, 70.4), = 0.025] among participants with, but not without, ASCVD [2.16 (-6.74, 11.5), = 1.000]. Non-esterified -palmitoleic acid (16:1n-7) was positively associated with FMD [19.7 (8.34, 31.0), = 0.024] among participants without, but not with ASCVD. No significant associations between NEFAs and estimated plaque thickness were observed. In older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for arteriopathy.

10aAged10aAged, 80 and over10aAtherosclerosis10aBiomarkers10aBrachial Artery10aCarotid Artery, Common10aCarotid Intima-Media Thickness10aDilatation10aFatty Acids, Monounsaturated10aFatty Acids, Nonesterified10aFemale10aHumans10aLinoleic Acid10aMale10aRegional Blood Flow10aRisk Factors10aUltrasonography1 aHuang, Neil, K1 aBůzková, Petra1 aMatthan, Nirupa, R1 aDjoussé, Luc1 aKizer, Jorge, R1 aMukamal, Kenneth, J1 aPolak, Joseph, F1 aLichtenstein, Alice, H uhttps://chs-nhlbi.org/node/891102793nas a2200253 4500008004100000022001400041245017100055210006900226260001600295520193800311100002102249700002102270700002702291700002302318700001902341700002002360700002202380700001802402700002002420700002102440700001802461700002402479856003602503 2022 eng d a1758-535X00aThe Associations of Individual and Subclasses of Non-Esterified Fatty Acids with Disability, and Mobility Limitation in Older Adults: the Cardiovascular Health Study.0 aAssociations of Individual and Subclasses of NonEsterified Fatty c2022 Sep 263 a

BACKGROUND: We sought to determine the associations between individual non-esterified fatty acids (NEFAs) and disability and mobility limitation.

METHODS: We studied 1734 participants in the Cardiovascular Health Study (CHS), an ongoing population-based cohort study of community-living older American adults. We measured 35 individual NEFA species in fasting serum samples obtained at the 1996-1997 clinic visit. Using yearly assessments of activities of daily living and self-reported mobility, we identified participants with incident disability or mobility limitation during 15 years of follow-up. Cox proportional hazards regression models were used to determine the associations between per-SD increment in the individual NEFAs and incident disability and mobility limitations with adjustment for potential confounding factors.

RESULTS: Higher concentrations of total and a broad range of individual NEFA species were associated with risk of disability and mobility limitation [disability: HR per SD of total NEFA (SD=174.70) =1.11, 95%CI=1.04-1.18, p=0.001; mobility limitation: HR per SD of total NEFA=1.09, 95%CI=1.02-1.16, p=0.01). Among individual saturated NEFAs (SFAs), myristic (14:0) and palmitic (16:0) acids were significantly associated with higher risk of both disability and mobility limitations, but longer-chain FAs were not. Most individual monounsaturated (MUFA), n-6 polyunsaturated fatty acids (PUFAs), and trans FAs were positively significantly associated with higher risks of both disability and mobility limitation. In contrast, most n-3 PUFA species were not associated with disability or mobility limitation.

CONCLUSIONS: Higher risks of disability and mobility limitation were observed for pro-inflammatory intermediate-chain SFAs, MUFAs, n-6 PUFAs, and trans FAs. Our findings indicated no significant association for anti-inflammatory n-3 PUFAs.

1 aAhiawodzi, Peter1 aBůzková, Petra1 aLichtenstein, Alice, H1 aMatthan, Nirupa, R1 aIx, Joachim, H1 aKizer, Jorge, R1 aTracy, Russell, P1 aArnold, Alice1 aNewman, Anne, B1 aSiscovick, David1 aDjoussé, Luc1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/9153