Sphingolipids and physical function in the Atherosclerosis Risk in Communities (ARIC) study.
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ABSTRACT:
SUBMITTER: Li D
PROVIDER: S-EPMC7806657 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Sphingolipids and physical function in the Atherosclerosis Risk in Communities (ARIC) study.
Li Danni D Alam Aniqa B AB Yu Fang F Kucharska-Newton Anna A Windham B Gwen BG Alonso Alvaro A
Scientific reports 20210113 1
Long-chain sphingomyelins (SMs) may play an important role in the stability of myelin sheath underlying physical function. The objective of this study was to examine the cross-sectional and longitudinal associations of long-chain SMs [SM (41:1), SM (41:2), SM (43:1)] and ceramides [Cer (41:1) and Cer (43:1)] with physical function in the Atherosclerosis Risk in Communities (ARIC) study. Plasma concentrations of SM (41:1), SM (41:2), SM (43:1), Cer (41:1) and Cer (43:1) were measured in 389 ARIC ...[more]
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Project description:BackgroundPlasma metabolites such as phosphatidylcholines and sphingomyelins (SMs) are associated with an age-related cognitive decline. However, their relations to age-related physical function decline remain largely unknown.MethodsWe examined the cross-sectional relations of 12 plasma metabolites (including four phosphatidylcholines and four SMs) with physical function in 383 older adults in the At herosclerosis Risk in Communities Study at the fifth exam (2011-2013, mean age [standard deviation (SD)]: 78.0 [5.5], 54.4% women, 28.3% African Americans). Physical function was assessed using grip strength, Short Physical Performance Battery, and 4-m walking speed. Individual metabolites were log-transformed and standardized. Multivariable linear regression was performed to account for demographics, APOE genotype, cardiovascular risk factors, comorbidities, use of antihypertensive and lipid-lowering medications, depressive symptoms, and cognition.ResultsLower concentrations of asymmetric dimethylarginine and higher concentrations of SM (OH) C22:1, SM (OH) C22:2, and SM (OH) C24:1 were associated with physical function measures. In particular, SM (OH) C22:1 and SM (OH) C24:1 were associated with all three measures of physical function: ?-coefficients (95% confidence interval) with grip strength were 0.89 kg (0.00, 1.78) and 0.86 kg (0.10, 1.61) per 1 SD higher concentration, respectively; with Short Physical Performance Battery score, were 0.61 (0.34, 0.88) and 0.41 (0.19, 0.63) per 1 SD difference, respectively; with 4-m walking speed were 0.035 m/s (0.013, 0.056) and 0.035 m/s (0.028, 0.047), respectively.ConclusionsPlasma SM (OH)s may be independently associated with physical function in older adults.
| S-EPMC6037051 | biostudies-literature
Project description:Background and aimsMost prior studies investigating the association of lower extremity peripheral artery disease (PAD) with physical function were small or analyzed selected populations (e.g., patients at vascular clinics or persons with reduced function), leaving particular uncertainty regarding the association in the general community.MethodsAmong 5262 ARIC participants (age 71-90 years during 2011-2013), we assessed the cross-sectional association of ankle-brachial index (ABI) with the Short Physical Performance Battery (SPPB) score (0-12), its individual components (chair stands, standing balance, and gait speed) (0-4 points each), and grip strength after accounting for potential confounders, including a history of coronary disease, stroke, or heart failure.ResultsThere were 411 participants (7.8%) with low ABI ≤0.90 and 469 (8.9%) participants with borderline low ABI 0.91-1.00. Both ABI ≤0.90 and 0.91-1.00 were independently associated with poor physical function (SPPB score ≤6) compared to ABI 1.11-1.20 (adjusted odds ratio 2.10 [95% CI 1.55-2.84] and 1.86 [1.38-2.51], respectively). The patterns were largely consistent across subgroups by clinical conditions (e.g., leg pain or other cardiovascular diseases), in every SPPB component, and for grip strength. ABI >1.3 (472 participants [9.0%]), indicative of non-compressible pedal arteries, was related to lower physical function as well but did not necessarily reach significance.ConclusionsIn community-dwelling older adults, low and borderline low ABI suggestive of PAD were independently associated with poorer systemic physical function compared to those with normal ABI. Clinical attention to PAD as a potential contributor to poor physical function is warranted in community-dwelling older adults.
| S-EPMC5325783 | biostudies-literature
Project description:People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers.Prospective cohort study.10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011.Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers.Fracture-related hospitalizations determined by diagnostic code.Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists.Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ?60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/?2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37).No bone mineral density assessment; one-time measurement of kidney function.Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation.
| S-EPMC4724513 | biostudies-literature
Project description:BackgroundFrail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals.Study designObservational study.Setting & participants4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013).PredictorsKidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C level (eGFRcys) and urine albumin-creatinine ratio.OutcomeFrailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity).Results341 (7%) participants were classified as frail, 1,475 (30%) had eGFRcr<60mL/min/1.73m2, 2,480 (50%) had eGFRcys<60mL/min/1.73m2, and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys<60mL/min/1.73m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and albumin-creatinine ratio. Frail individuals with eGFRcr of 60 to <75mL/min/1.73m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants).LimitationsCross-sectional study design.ConclusionsFrail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.
| S-EPMC5263025 | biostudies-literature
Project description:BackgroundPhysical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline.MethodsThis prospective cohort included 5 481 older adults aged 67-91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45-64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1-4.ResultsThe average adjusted rate of SPPB decline (points per 5 years) for older adults was -0.79 (confidence interval [CI]: -0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of -0.47, 95% CI: -0.64, -0.30), diabetes (+73% decline vs no diabetes: additional decline of -0.67, 95% CI: -1.09, -0.24), elevated systolic blood pressure (+17% decline per SD: -0.16, 95% CI: -0.23, -0.10), and elevated fasting blood glucose (+16% decline per SD: -0.015, 95% CI: -0.24, -0.06). Each decade greater mid-life exposure to hypertension (+32% decline: -0.93, 95% CI: -1.25, -0.61) and diabetes (+35% decline: -1.03, 95% CI: -1.68, -0.38) was associated with faster SPPB decline.ConclusionsMid-life control of blood pressure and diabetes may offset aging-related functional decline.
| S-EPMC10809050 | biostudies-literature
Project description:BACKGROUND:Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD). STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:14,946 participants aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through 2012. PREDICTORS:Race- and sex-specific quartiles of percent-predicted forced vital capacity (FVC) and the proportion of forced expiratory volume in 1 second of expiration to FVC (FEV1/FVC) at baseline determined with spirometry. OUTCOMES:Incident ESRD (defined here as renal replacement therapy or death due to CKD) as the primary outcome and incident CKD (defined here as ESRD, ?25% decline in estimated glomerular filtration rate to a level <60mL/min/1.73m2, or CKD-related hospitalizations/deaths) as the secondary outcome. RESULTS:During a median follow-up of 23.6 years, 526 (3.5%) participants developed ESRD. After adjusting for potential confounders, the cause-specific HR of incident ESRD for the lowest (vs highest) quartile was 1.72 (95% CI, 1.31-2.26) for percent-predicted FVC and 1.33 (95% CI, 1.03-1.73) for FEV1/FVC. Compared to a high-normal lung function pattern, a mixed pattern (ie, percent-predicted FVC<80% and FEV1/FVC<70%; 3.4% of participants) demonstrated the highest adjusted cause-specific HR of ESRD at 2.28 (95% CI, 1.50-3.45), followed by the restrictive pattern (ie, percent-predicted FVC<80% and FEV1/FVC?70%; 4.8% of participants) at 2.03 (95% CI, 1.47-2.81), obstructive pattern (ie, percent-predicted FVC?80% and FEV1/FVC<70%; 18.9% of participants) at 1.47 (95% CI, 1.09-1.99), and low-normal pattern (ie, percent-predicted FVC 80%-<100% and FEV1/FVC?70%, or percent-predicted FVC?80% and FEV1/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar associations were seen with incident CKD. LIMITATIONS:Limited number of participants with moderate/severe lung dysfunction and spirometry only at baseline. CONCLUSIONS:Reduced lung function, particularly lower percent-predicted FVC, is independently associated with CKD progression. Our findings suggest a potential pathophysiologic contribution of reduced lung function to the development of CKD and a need for monitoring kidney function in persons with reduced lung function.
| S-EPMC5651181 | biostudies-literature
Project description:<p>The Atherosclerosis Risk in Communities (ARIC) Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a prospective epidemiologic study conducted in four U.S. communities. The four communities are Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date.</p> <p>ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort.</p> <p>In the Community Surveillance Component, currently ongoing, these four communities are investigated to determine the community-wide occurrence of hospitalized myocardial infarction and coronary heart disease deaths in men and women aged 35-84 years. Hospitalized stroke is investigated in cohort participants only. Starting in 2006, the study conducts community surveillance of inpatient (ages 55 years and older) and outpatient heart failure (ages 65 years and older) for heart failure events beginning in 2005.</p> <p>ARIC is currently funded through January 31, 2012.</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to atherosclerosis and cardiovascular disease through large-scale genome-wide association studies of well-characterized cohorts of adults in four defined populations. Genotyping was performed at the Broad Institute of MIT and Harvard, a GENEVA genotyping center. Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>
| phs000090.v1.p1 | EGA
Project description:ObjectiveTo explore the association of intracranial atherosclerotic disease (ICAD) with mild cognitive impairment (MCI) and dementia.MethodsFrom 2011 to 2013, 1,744 participants completed high-resolution vessel wall MRI from the population-based Atherosclerosis Risk in Communities Study by a sampling strategy that allowed weighting back to the cohort. We defined ICAD by plaque features (presence, territory, stenosis, number). Trained clinicians used an algorithm incorporating information from interviews and neuropsychological and neurologic examinations to adjudicate for MCI and dementia. We determined the relative prevalence ratio (RPR) of MCI or dementia after adjusting for risk factors at midlife using multinomial logistic regression.ResultsA total of 601 (34.5%) participants had MCI (mean age ± SD, 76.6 ± 5.2 years), 83 (4.8%) had dementia (79.1 ± 5.3 years), and 857 (49.1%) were current or former smokers. Anterior cerebral artery (ACA) plaque (adjusted RPR 3.81, 95% confidence interval [CI] 1.57-9.23), >2 territories with plaque (adjusted RPR 2.12, 95% CI 1.00-4.49), and presence of stenosis >50% (adjusted RPR 1.92, 95% CI 1.01-3.65) were associated with increased prevalence of dementia in separate models. Posterior cerebral artery plaque was associated with MCI but did not reach statistical significance for dementia (adjusted RPR MCI 1.43, 95% CI 1.04-1.98; adjusted RPR dementia 1.58, 95% CI 0.79-2.85). There were no associations with middle cerebral artery atherosclerotic lesions or cognitive impairment. Many participants had plaque in >1 territory (n = 291, 46%) and participants with ACA plaques (n = 69) had the greatest number of plaques in other territories (mean 6.0, SD 4.4).ConclusionsThis study demonstrates associations between ICAD and clinical MCI and dementia.
| S-EPMC5395073 | biostudies-literature
Project description:BACKGROUND:Reduced estimated glomerular filtration rate (eGFR) and elevated urinary albumin-to-creatinine ratio (ACR) individually increase risk of cardiovascular disease (CVD). We hypothesized that these associations are stronger among people with abnormal (both low and high) hemoglobin levels. METHODS AND RESULTS:Using 5801 participants with available hemoglobin measures of the ARIC (Atherosclerosis Risk in Community) study in 1996-1998, we explored the cross-sectional association of eGFR and ACR with hemoglobin levels and their longitudinal associations with CVD (heart failure, coronary heart disease, and stroke) risk through 2013. At baseline, 8.8% had anemia (<13 g/dL in men and <12 g/dL in women) and 7.2% had high hemoglobin (?16 g/dL in men and ?15 g/dL in women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence interval, 1.59-2.82) for eGFR 30 to 59 compared with ?90 mL/min per 1.73 m2 and 1.45 (1.07-1.95) for ACR ?30 compared with <10 mg/g. ACR ?30 mg/g was also associated with high hemoglobin (prevalence ratio, 1.57 [1.12-2.19] compared with <10 mg/g). During follow-up, there were 1069 incident CVDs among 5098 CVD-free participants at baseline. In multivariable Cox models, lower eGFR, higher ACR, and anemia were each independently associated with CVD risk, with the association of low eGFR being slightly stronger in anemia (P-for-interaction, 0.072). There was no hemoglobin-ACR interaction; however, when CVD subtypes were analyzed separately, risk of coronary heart disease and stroke associated with high ACR was slightly stronger in high hemoglobin (P-for-interaction, 0.074). CONCLUSIONS:Kidney function, albuminuria, and anemia were correlated and independently associated with CVD risk. Correlation and potential interaction for atherosclerotic CVD between albuminuria and high hemoglobin deserve further investigation.
| S-EPMC5850152 | biostudies-literature
Project description:RATIONALE & OBJECTIVE:The relationship between hypertension, antihypertension medication use, and change in glomerular filtration rate (GFR) over time among individuals with preserved GFR requires investigation. STUDY DESIGN:Observational study. SETTING & PARTICIPANTS:14,854 participants from the Atherosclerosis Risk in Communities (ARIC) Study. PREDICTORS:Baseline hypertension status (1987-1989) was categorized according to the 2017 American College of Cardiology/American Heart Association Clinical Practice Guideline as normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication. OUTCOMES:Slope of estimated GFR (eGFR) at 5 study visits over 30 years. ANALYTICAL APPROACH:Mixed models with random intercepts and random slopes were fit to evaluate the association between baseline hypertension status and slope of eGFR. RESULTS:At baseline, 13.2%, 7.3%, and 19.4% of whites and 15.8%, 14.9%, and 39.9% of African Americans had stage 1 hypertension, stage 2 hypertension without medication, and stage 2 hypertension with medication. Compared with those with normal blood pressure, the annual eGFR decline was greater in people with higher blood pressure (whites: elevated blood pressure, -0.11mL/min/1.73m2; stage 1 hypertension, -0.15mL/min/1.73m2; stage 2 hypertension without medication, -0.36mL/min/1.73m2; stage 2 hypertension with medication, -0.17mL/min/1.73m2; African Americans: elevated blood pressure, -0.21mL/min/1.73m2; stage 1 hypertension, -0.16mL/min/1.73m2; stage 2 hypertension without medication, -0.50mL/min/1.73m2; stage 2 hypertension with medication, -0.16mL/min/1.73m2). The 30-year predicted probabilities of developing chronic kidney disease stage G3a+with normal blood pressure, elevated blood pressure, stage 1 hypertension, stage 2 hypertension without medication, or stage 2 hypertension with medication among whites were 54.4%, 61.6%, 64.7%, 78.1%, and 70.9%, respectively, and 55.4%, 62.8%, 60.9%, 76.1%, and 66.6% among African Americans. LIMITATIONS:Slope estimated using a maximum of 5 eGFR assessments; differential loss to follow-up. CONCLUSIONS:Compared to normotension, baseline hypertension status was associated with faster kidney function decline over 30-year follow-up in a general population cohort. This difference was attenuated among people using antihypertensive medications.
| S-EPMC6760841 | biostudies-literature