02863nas a2200265 4500008004100000022001400041245018900055210006900244260001600313300001200329490000600341520197900347100002002326700002902346700001502375700001802390700001902408700001902427700002002446700002402466700002202490700002402512700002502536856003602561 2019 eng d a2047-998000aSerial Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway and Total Mortality, Cause-Specific Mortality, and Cardiovascular Diseases in the Cardiovascular Health Study.0 aSerial Plasma Phospholipid Fatty Acids in the De Novo Lipogenesi c2019 Nov 19 ae0128810 v83 a

Background Synthesized fatty acids (FAs) from de novo lipogenesis may affect cardiometabolic health, but longitudinal associations between serially measured de novo lipogenesis-related fatty acid biomarkers and mortality or cardiovascular disease (CVD) are not well established. Methods and Results We investigated longitudinal associations between de novo lipogenesis-related fatty acids with all-cause mortality, cause-specific mortality, and incident CVD among 3869 older US adults, mean (SD) age 75 (5) years and free of prevalent CVD at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), oleic acid (18:1n-9), and other risk factors were serially measured at baseline, 6 years, and 13 years. All-cause mortality, cause-specific mortality, and incident fatal and nonfatal CVD were centrally adjudicated. Risk was assessed in multivariable-adjusted Cox models with time-varying FAs and covariates. During 13 years, median follow-up (maximum 22.4 years), participants experienced 3227 deaths (1131 CVD, 2096 non-CVD) and 1753 incident CVD events. After multivariable adjustment, higher cumulative levels of 16:0, 16:1n-7, and 18:1n-9 were associated with higher all-cause mortality, with extreme-quintile hazard ratios (95% CIs) of 1.35 (1.17-1.56), 1.40 (1.21-1.62), and 1.56 (1.35-1.80), respectively, whereas higher levels of 18:0 were associated with lower mortality (hazard ratio=0.76; 95% CI=0.66-0.88). Associations were generally similar for CVD mortality versus non-CVD mortality, as well as total incident CVD. Changes in levels of 16:0 were positively, and 18:0 inversely, associated with all-cause mortality (hazard ratio=1.23, 95% CI=1.08-1.41; and hazard ratio=0.78, 95% CI=0.68-0.90). Conclusions Higher long-term levels of 16:0, 16:1n-7, and 18:1n-9 and changes in 16:0 were positively, whereas long-term levels and changes in 18:0 were inversely, associated with all-cause mortality in older adults.

1 aLai, Heidi, T M1 aOtto, Marcia, C de Olive1 aLee, Yujin1 aH Y Wu, Jason1 aSong, Xiaoling1 aKing, Irena, B1 aPsaty, Bruce, M1 aLemaitre, Rozenn, N1 aMcKnight, Barbara1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/827502761nas a2200265 4500008004100000022001400041245013400055210006900189260001600258300001200274490000600286520192700292100001502219700002002234700002902254700002402283700002202307700001902329700001902348700002302367700002002390700002402410700002502434856003602459 2020 eng d a2047-998000aSerial Biomarkers of De Novo Lipogenesis Fatty Acids and Incident Heart Failure in Older Adults: The Cardiovascular Health Study.0 aSerial Biomarkers of De Novo Lipogenesis Fatty Acids and Inciden c2020 Feb 18 ae0141190 v93 a

Background De novo lipogenesis (DNL) is an endogenous pathway that converts excess dietary starch, sugar, protein, and alcohol into specific fatty acids (FAs). Although elevated DNL is linked to several metabolic abnormalities, little is known about how long-term habitual levels and changes in levels of FAs in the DNL pathway relate to incident heart failure (HF). Methods and Results We investigated whether habitual levels and changes in serial measures of FAs in the DNL pathway were associated with incident HF among 4249 participants free of HF at baseline. Plasma phospholipid FAs were measured at baseline, 6 years, and 13 years using gas chromatography, and risk factors for HF were measured using standardized methods. Incident HF was centrally adjudicated using medical records. We prospectively evaluated associations with HF risk of (1) habitual FA levels, using cumulative updating to assess long-term exposure, and (2) changes in FA levels over time. During 22.1 years of follow-up, 1304 HF cases occurred. After multivariable adjustment, habitual levels and changes in levels of palmitic acid (16:0) were positively associated with incident HF (interquintile hazard ratio [95% CI]=1.17 [1.00-1.36] and 1.26 [1.03-1.55], respectively). Changes in levels of 7-hexadecenoic acid (16:1n-9) and vaccenic acid (18:1n-7) were each positively associated with risk of HF (1.36 [1.13-1.62], and 1.43 [1.18-1.72], respectively). Habitual levels and changes in levels of myristic acid (14:0), palmitoleic acid (16:1n-7), stearic acid (18:0), and oleic acid (18:1n-9) were not associated with incident HF. Conclusions Both habitual levels and changes in levels of 16:0 were positively associated with incident HF in older adults. Changes in 16:1n-9 and 18:1n-7 were also positively associated with incident HF. These findings support a potential role of DNL or these DNL-related FAs in the development of HF.

1 aLee, Yujin1 aLai, Heidi, T M1 aOtto, Marcia, C de Olive1 aLemaitre, Rozenn, N1 aMcKnight, Barbara1 aKing, Irena, B1 aSong, Xiaoling1 aHuggins, Gordon, S1 aVest, Amanda, R1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/824103651nas a2200313 4500008004100000022001400041245015000055210006900205260001600274300001200290520265600302100001502958700001502973700001702988700002003005700002903025700002403054700002203078700002203100700002003122700002403142700002203166700002203188700002003210700002403230700002203254700002503276856003603301 2021 eng d a2047-998000aLongitudinal Plasma Measures of Trimethylamine N-Oxide and Risk of Atherosclerotic Cardiovascular Disease Events in Community-Based Older Adults.0 aLongitudinal Plasma Measures of Trimethylamine NOxide and Risk o c2021 Aug 16 ae0206463 a

Background Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite of dietary choline, L-carnitine, and phosphatidylcholine-rich foods. On the basis of experimental studies and patients with prevalent disease, elevated plasma TMAO may increase risk of atherosclerotic cardiovascular disease (ASCVD). TMAO is also renally cleared and may interact with and causally contribute to renal dysfunction. Yet, how serial TMAO levels relate to incident and recurrent ASCVD in community-based populations and the potential mediating or modifying role of renal function are not established. Methods and Results We investigated associations of serial measures of plasma TMAO, assessed at baseline and 7 years, with incident and recurrent ASCVD in a community-based cohort of 4131 (incident) and 1449 (recurrent) older US adults. TMAO was measured using stable isotope dilution liquid chromatography-tandem mass spectrometry (laboratory coefficient of variation, <6%). Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was centrally adjudicated using medical records. Risk was assessed by multivariable Cox proportional hazards regression, including time-varying demographics, lifestyle factors, medical history, laboratory measures, and dietary habits. Potential mediating effects and interaction by estimated glomerular filtration rate (eGFR) were assessed. During prospective follow-up, 1766 incident and 897 recurrent ASCVD events occurred. After multivariable adjustment, higher levels of TMAO were associated with a higher risk of incident ASCVD, with extreme quintile hazard ratio (HR) compared with the lowest quintile=1.21 (95% CI, 1.02-1.42; -trend=0.029). This relationship appeared mediated or confounded by eGFR (eGFR-adjusted HR, 1.07; 95% CI, 0.90-1.27), as well as modified by eGFR (-interaction <0.001). High levels of TMAO were associated with higher incidence of ASCVD in the presence of impaired renal function (eGFR <60 mL/min per 1.73 m: HR, 1.56 [95% CI, 1.13-2.14]; -trend=0.007), but not normal or mildly reduced renal function (eGFR ≥60 mL/min per 1.73 m: HR, 1.03 [95% CI, 0.85-1.25]; -trend=0.668). Among individuals with prior ASCVD, TMAO associated with higher risk of recurrent ASCVD (HR, 1.25 [95% CI, 1.01-1.56]; -trend=0.009), without significant modification by eGFR. Conclusions In this large community-based cohort of older US adults, serial measures of TMAO were associated with higher risk of incident ASCVD, with apparent modification by presence of impaired renal function and with higher risk of recurrent ASCVD.

1 aLee, Yujin1 aNemet, Ina1 aWang, Zeneng1 aLai, Heidi, T M1 aOtto, Marcia, C de Olive1 aLemaitre, Rozenn, N1 aFretts, Amanda, M1 aSotoodehnia, Nona1 aBudoff, Matthew1 aDiDonato, Joseph, A1 aMcKnight, Barbara1 aTang, W, H Wilson1 aPsaty, Bruce, M1 aSiscovick, David, S1 aHazen, Stanley, L1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/883104438nas a2200457 4500008004100000022001400041245009000055210006900145260001500214300001300229490000600242520319000248653000903438653001203447653002803459653001403487653001203501653001903513653001103532653001103543653000903554653001703563653002403580100002203604700002203626700001703648700002003665700002403685700001503709700002903724700002403753700001503777700002003792700002403812700002203836700002203858700001503880700002403895700002503919856003603944 2022 eng d a2574-380500aAssociation of Trimethylamine N-Oxide and Metabolites With Mortality in Older Adults.0 aAssociation of Trimethylamine NOxide and Metabolites With Mortal c2022 05 02 ae22132420 v53 a

Importance: Little is known about the association of trimethylamine N-oxide (TMAO), a novel plasma metabolite derived from L-carnitine and phosphatidylcholine, and related metabolites (ie, choline, betaine, carnitine, and butyrobetaine) with risk of death among older adults in the general population.

Objective: To investigate the associations of serial measures of plasma TMAO and related metabolites with risk of total and cause-specific death (ie, deaths from cardiovascular diseases [CVDs] and non-CVDs) among older adults in the US.

Design, Setting, and Participants: This prospective cohort study involved 5333 participants from the Cardiovascular Health Study-a community-based longitudinal cohort of adults aged 65 years or older-who were followed up from June 1, 1989, to December 31, 2015. Participants were from 4 communities in the US (Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania). Data were analyzed from March 17 to June 23, 2021.

Exposures: Plasma TMAO, choline, betaine, carnitine, and butyrobetaine levels were measured using stored samples from baseline (June 1, 1989, to May 31, 1990, or November 1, 1992, to June 31, 1993) and follow-up examination (June 1, 1996, to May 31, 1997). Measurements were performed through stable-isotope dilution liquid chromatography with tandem mass spectrometry using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry.

Main Outcomes and Measures: Deaths (total and cause specific) were adjudicated by a centralized Cardiovascular Health Study events committee based on information from medical records, laboratory and diagnostic reports, death certificates, and/or interviews with next of kin. The associations of each metabolite with mortality were assessed using Cox proportional hazards regression models.

Results: Among 5333 participants in the analytic sample, the mean (SD) age was 73 (6) years; 2149 participants (40.3%) were male, 3184 (59.7%) were female, 848 (15.9%) were African American, 4450 (83.4%) were White, and 35 (0.01%) were of other races (12 were American Indian or Alaska Native, 4 were Asian or Pacific Islander, and 19 were of other races or ethnicities). During a median follow-up of 13.2 years (range, 0-26.9 years), 4791 deaths occurred. After adjustment for potential confounders, the hazard ratios for death from any cause (ie, total mortality) comparing extreme quintiles (fifth vs first) of plasma concentrations were 1.30 (95% CI, 1.17-1.44) for TMAO, 1.19 (95% CI, 1.08-1.32) for choline, 1.26 (95% CI, 1.15-1.40) for carnitine, and 1.26 (95% CI, 1.13-1.40) for butyrobetaine. Plasma betaine was not associated with risk of death. The extent of risk estimates was similar for CVD and non-CVD mortality.

Conclusions and Relevance: In this cohort study, plasma concentrations of TMAO and related metabolites were positively associated with risk of death. These findings suggest that circulating TMAO is an important novel risk factor associated with death among older adults.

10aAged10aBetaine10aCardiovascular Diseases10aCarnitine10aCholine10aCohort Studies10aFemale10aHumans10aMale10aMethylamines10aProspective Studies1 aFretts, Amanda, M1 aHazen, Stanley, L1 aJensen, Paul1 aBudoff, Matthew1 aSitlani, Colleen, M1 aWang, Meng1 aOtto, Marcia, C de Olive1 aDiDonato, Joseph, A1 aLee, Yujin1 aPsaty, Bruce, M1 aSiscovick, David, S1 aSotoodehnia, Nona1 aTang, W, H Wilson1 aLai, Heidi1 aLemaitre, Rozenn, N1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/909103344nas a2200421 4500008004100000022001400041245015100055210006900206260001200275300001400287490000700301520211000308653001202418653002002430653002802450653001402478653001102492653000902503653001702512653001702529100001502546700001702561700001502578700002002593700002902613700002402642700001902666700002202685700002002707700002402727700002202751700002202773700002002795700002402815700002202839700002502861856003602886 2022 eng d a1524-463600aDietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study.0 aDietary Meat Trimethylamine NOxideRelated Metabolites and Incide c2022 09 ae273-e2880 v423 a

BACKGROUND: Effects of animal source foods (ASF) on atherosclerotic cardiovascular disease (ASCVD) and underlying mechanisms remain controversial. We investigated prospective associations of different ASF with incident ASCVD and potential mediation by gut microbiota-generated trimethylamine N-oxide, its L-carnitine-derived intermediates γ-butyrobetaine and crotonobetaine, and traditional ASCVD risk pathways.

METHODS: Among 3931 participants from a community-based US cohort aged 65+ years, ASF intakes and trimethylamine N-oxide-related metabolites were measured serially over time. Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, other atherosclerotic death) was adjudicated over 12.5 years median follow-up. Cox proportional hazards models with time-varying exposures and covariates examined ASF-ASCVD associations; and additive hazard models, mediation proportions by different risk pathways.

RESULTS: After multivariable-adjustment, higher intakes of unprocessed red meat, total meat, and total ASF associated with higher ASCVD risk, with hazard ratios (95% CI) per interquintile range of 1.15 (1.01-1.30), 1.22 (1.07-1.39), and 1.18 (1.03-1.34), respectively. Trimethylamine N-oxide-related metabolites together significantly mediated these associations, with mediation proportions (95% CI) of 10.6% (1.0-114.5), 7.8% (1.0-32.7), and 9.2% (2.2-44.5), respectively. Processed meat intake associated with a nonsignificant trend toward higher ASCVD (1.11 [0.98-1.25]); intakes of fish, poultry, and eggs were not significantly associated. Among other risk pathways, blood glucose, insulin, and C-reactive protein, but not blood pressure or blood cholesterol, each significantly mediated the total meat-ASCVD association.

CONCLUSIONS: In this large, community-based cohort, higher meat intake associated with incident ASCVD, partly mediated by microbiota-derived metabolites of L-carnitine, abundant in red meat. These novel findings support biochemical links between dietary meat, gut microbiome pathways, and ASCVD.

10aAnimals10aAtherosclerosis10aCardiovascular Diseases10aCarnitine10aHumans10aMeat10aMethylamines10aRisk Factors1 aWang, Meng1 aWang, Zeneng1 aLee, Yujin1 aLai, Heidi, T M1 aOtto, Marcia, C de Olive1 aLemaitre, Rozenn, N1 aFretts, Amanda1 aSotoodehnia, Nona1 aBudoff, Matthew1 aDiDonato, Joseph, A1 aMcKnight, Barbara1 aTang, W, H Wilson1 aPsaty, Bruce, M1 aSiscovick, David, S1 aHazen, Stanley, L1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/918202819nas a2200289 4500008004100000022001400041245015800055210006900213260001600282520189100298100002902189700001802218700001702236700002102253700002002274700002502294700001502319700001502334700001502349700001902364700002402383700002202407700001702429700002202446700002502468856003602493 2022 eng d a1875-890800aLongitudinal Associations of Plasma TMAO and Related Metabolites with Cognitive Impairment and Dementia in Older Adults: The Cardiovascular Health Study.0 aLongitudinal Associations of Plasma TMAO and Related Metabolites c2022 Sep 023 a

BACKGROUND: Animal studies suggest that gut microbiome metabolites such as trimethylamine N-oxide (TMAO) may influence cognitive function and dementia risk. However potential health effects of TMAO and related metabolites remain unclear.

OBJECTIVE: We examined prospective associations of TMAO, γ-butyrobetaine, crotonobetaine, carnitine, choline, and betaine with risk of cognitive impairment and dementia among older adults aged 65 years and older in the Cardiovascular Health Study (CHS).

METHODS: TMAO and metabolites were measured in stored plasma specimens collected at baseline. Incident cognitive impairment was assessed using the 100-point Modified Mini-Mental State Examination administered serially up to 7 times. Clinical dementia was identified using neuropsychological tests adjudicated by CHS Cognition Study investigators, and by ICD-9 codes from linked Medicare data. Associations of each metabolite with cognitive outcomes were assessed using Cox proportional hazards models.

RESULTS: Over a median of 13 years of follow-up, 529 cases of cognitive impairment, and 522 of dementia were identified. After multivariable adjustment for relevant risk factors, no associations were seen with TMAO, carnitine, choline, or betaine. In contrast, higher crotonobetaine was associated with 20-32% higher risk of cognitive impairment and dementia per interquintile range (IQR), while γ-butyrobetaine was associated with ∼25% lower risk of the same cognitive outcomes per IQR.∥Conclusion:These findings suggest that γ-butyrobetaine, crotonobetaine, two gut microbe and host metabolites, are associated with risk of cognitive impairment and dementia. Our results indicate a need for mechanistic studies evaluating potential effects of these metabolites, and their interconversion on brain health, especially later in life.

1 aOtto, Marcia, C de Olive1 aLi, Xinmin, S1 aWang, Zeneng1 aSiscovick, David1 aNewman, Anne, B1 aLai, Heidi, Tsz Mung1 aNemet, Ina1 aLee, Yujin1 aWang, Meng1 aFretts, Amanda1 aLemaitre, Rozenn, N1 aTang, W, H Wilson1 aLopez, Oscar1 aHazen, Stanley, L1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/915703034nas a2200409 4500008004100000022001400041245011900055210006900174260001200243300001100255490000800266520189800274653002702172653000902199653001702208653001102225653001802236653001102254653000902265653001702274653001702291100002002308700002102328700002402349700001702373700001502390700002302405700002002428700002002448700001502468700002102483700001502504700002202519700002502541700002202566856003602588 2022 eng d a1873-276300aTrimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study.0 aTrimethylamine Noxide and hip fracture and bone mineral density  c2022 08 a1164310 v1613 a

CONTEXT: Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) may adversely affect bone by inducing oxidative stress. Whether this translates into increased fracture risk in older adults is uncertain.

OBJECTIVE: Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults.

DESIGN AND SETTING: Cox hazard models and linear regression stratified by sex examined the associations of TMAO with hip fracture and BMD in the longitudinal cohort of the Cardiovascular Health Study.

PARTICIPANTS: 5019 U.S. adults aged ≥65 years.

EXPOSURE: Plasma TMAO.

MAIN OUTCOME MEASURES: Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n = 1400).

RESULTS: Six hundred sixty-six incident hip fractures occurred during up to 26 years of follow-up (67,574 person-years). After multivariable adjustment, TMAO was not significantly associated with hip fracture (women: hazard ratio (HR) [95% confidence interval (CI)] of 1.00[0.92,1.09] per TMAO doubling; men: 1.12[0.95,1.33]). TMAO was also not associated with total hip BMD (women: BMD difference [95% CI] of 0.42 g/cm*100 [-0.34,1.17] per TMAO doubling; men: 0.19[-1.04,1.42]). In exploratory analyses, we found an interaction between body mass index (BMI) and the association of TMAO with hip fracture (P < 0.01). Higher TMAO was significantly associated with risk of hip fracture in adults with overweight or obesity (BMI ≥ 25) (HR [95% CI]:1.17[1.05,1.31]), but not normal or underweight.

CONCLUSIONS: Among older US men and women, TMAO was not significantly associated with risk of hip fracture or BMD overall. Exploratory analyses suggested a significant association between higher TMAO and hip fracture when BMI was elevated, which merits further study.

10aAbsorptiometry, Photon10aAged10aBone Density10aFemale10aHip Fractures10aHumans10aMale10aMethylamines10aRisk Factors1 aElam, Rachel, E1 aBůzková, Petra1 aBarzilay, Joshua, I1 aWang, Zeneng1 aNemet, Ina1 aBudoff, Matthew, J1 aCauley, Jane, A1 aFink, Howard, A1 aLee, Yujin1 aRobbins, John, A1 aWang, Meng1 aHazen, Stanley, L1 aMozaffarian, Dariush1 aCarbone, Laura, D uhttps://chs-nhlbi.org/node/908903419nas a2200349 4500008004100000022001400041245010000055210006900155260001600224520237600240100001502616700002202631700001802653700002902671700001502700700002402715700001902739700001502758700002202773700002402795700002002819700002402839700001702863700001802880700002402898700002002922700002402942700002002966700002502986700002203011856003603033 2024 eng d a1533-345000aThe Gut Microbial Metabolite Trimethylamine N-oxide, Incident CKD, and Kidney Function Decline.0 aGut Microbial Metabolite Trimethylamine Noxide Incident CKD and  c2024 Apr 093 a

BACKGROUND: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes kidney injury and tubulointerstitial fibrosis. Little is known about prospective associations between TMAO and kidney outcomes, especially incident CKD. We hypothesized that higher plasma TMAO levels would be associated with higher risk of incident CKD and greater rate of kidney function decline.

METHODS: We included 10,564 participants from two community-based, prospective cohorts with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 to assess incident CKD. TMAO was measured using targeted mass spectrometry at baseline and one follow-up visit. Creatinine and Cystatin C were measured up to 4 times during follow-up and used to compute eGFR. Incident CKD was defined as an eGFR decline ≥ 30% from baseline and a resulting eGFR<60 ml/min/1.73 m2. Time-varying Cox models assessed the association of serial TMAO measures with incident CKD, adjusting for sociodemographic, lifestyle, diet, and cardiovascular disease risk factors. Linear mixed models assessed the association with annualized eGFR change in 10,009 participants with at least one follow-up eGFR measure without exclusions for baseline eGFR levels.

RESULTS: During a median follow-up of 9.4 years (interquartile range: 9.1-11.6 years), 979 incident CKD events occurred. Higher TMAO levels associated with higher risk of incident CKD (2nd to 5th vs. 1st quintile HR[95%CI]= 1.65 [1.22-2.23], 1.68 [1.26-2.25], 2.28 [1.72-3.02], and 2.24[1.68-2.98], respectively) and greater annualized eGFR decline ( 2nd to 5th vs. 1st quintile annualized eGFR change= -0.21 [-0.32, -0.09], -0.17 [-0.29, -0.05], -0.35 [-0.47, -0.22], and -0.43[-0.56, -0.30], respectively) with monotonic dose-response relationships. These associations were consistent across different racial/ethnic groups examined. The association with eGFR decline was similar to or larger than that seen for established CKD risk factors including diabetes, per 10 mmHg of higher systolic blood pressure, per 10 years of older age, and Black race.

CONCLUSIONS: In community-based US adults, higher serial measures of plasma TMAO were associated with higher risk of incident CKD and greater annualized kidney function decline.

1 aWang, Meng1 aTang, W, H Wilson1 aLi, Xinmin, S1 aOtto, Marcia, C de Olive1 aLee, Yujin1 aLemaitre, Rozenn, N1 aFretts, Amanda1 aNemet, Ina1 aSotoodehnia, Nona1 aSitlani, Colleen, M1 aBudoff, Matthew1 aDiDonato, Joseph, A1 aWang, Zeneng1 aBansal, Nisha1 aShlipak, Michael, G1 aPsaty, Bruce, M1 aSiscovick, David, S1 aSarnak, Mark, J1 aMozaffarian, Dariush1 aHazen, Stanley, L uhttps://chs-nhlbi.org/node/9648