Kidney Function and Subclinical Arrhythmias: The Multi-Ethnic Study of Atherosclerosis.
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ABSTRACT:
SUBMITTER: Wiggins KL
PROVIDER: S-EPMC8664740 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and aimsSubclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds.MethodsThe associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10(-4) (0.05/66).ResultsIn EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10(-9); rs4977574, P = 4 × 10(-9)), COL4A1 (rs9515203, P = 9 × 10(-6)), and PHACTR1 (rs9349379, P = 4 × 10(-4)). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10(-5); rs4977574, P = 5 × 10(-5)), APOA5 (rs964184, P = 2 × 10(-4)), and ADAMTS7 (rs7173743, P = 4 × 10(-4)). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN.ConclusionOur results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations.
| S-EPMC4738145 | biostudies-literature
Project description:A major limitation of past work on the social patterning of atherosclerosis has been the reliance on measures of neighborhood or individual-level socioeconomic position (SEP) assessed at a single point in time in adulthood. Risk of chronic disease is thought to accumulate throughout the life-course, so the use of a measure for a single point in time may result in inaccurate estimates of the social patterning of subclinical disease. Using data from the US Multi-Ethnic Study of Atherosclerosis (MESA), we examined the relation between childhood SEP [CSEP] (father or caretaker's education), adulthood SEP [ASEP] (a summary score of income, education, and wealth), and 20-year average exposure to neighborhood poverty [NSEP] (residential addresses geocoded and linked to census data) and the prevalence of subclinical atherosclerosis, as assessed by common carotid intimal-medial thickness (IMT) in mid to late adulthood. Participants were 45-84 years of age at baseline and were sampled from six study sites in the United States. After adjustment for age, CSEP and ASEP were both inversely and independently associated with IMT in men. All three indicators CSEP, ASEP, and NSEP were inversely and independently associated with IMT in women. Associations were somewhat reduced after adjustment for cardiovascular risk factors, suggesting that these factors may play a mediating role. There was evidence of heterogeneity in effects of NSEP by gender, and in the effects of ASEP and NSEP by race/ethnicity. Our results contribute to the growing body of work that shows that SEP at multiple points in the life-course, and at the individual and neighborhood level, contributes to the development of atherosclerosis.
| S-EPMC5444463 | biostudies-literature
Project description:Background and Purpose- Many health effects of sleep apnea (SA) may be mediated through accelerated atherosclerosis. We examined the associations of snoring and several measurements of SA with subclinical carotid atherosclerosis in a large multiethnic population sample. Methods- This analysis included 1615 participants (mean age, 68 years) from examination 5 (2010-2013) of the MESA study (Multi-Ethnic Study of Atherosclerosis). Sleep measures including SA (apnea-hypopnea index [4%], ≥15 events/hour) were derived from full in-home polysomnography. Carotid atherosclerosis was measured using high-resolution B-mode ultrasound. Multivariable linear and logistic regression models were used to evaluate the associations between sleep exposures with carotid intima-media thickness and the presence of carotid plaque, respectively. Effect modification by age, sex, and race/ethnicity was examined. Results- In multivariable analysis, SA was associated with an increased odds of carotid plaque presence in individuals aged <68 years (odds ratio, 1.47; 95% CI, 1.05-2.06) but not in older individuals (odds ratio, 0.95; 95% CI, 0.67-1.37; P interaction=0.078). Greater hypoxemia (sleep time <90% saturation) was associated with increasing carotid intima-media thickness in younger (0.028±0.014 mm) but not in older individuals (-0.001±0.013 mm; P interaction=0.106). Self-reported snoring was not associated with carotid atherosclerosis. In assessing race-specific outcomes, greater hypoxemia was associated with increased carotid intima-media thickness in blacks (0.049±0.017 mm; P interaction=0.033). Conclusions- In this large multiethnic population-based sample, sleep disturbances are associated with subclinical carotid atherosclerosis in both men and women, particularly in those <68 years of age. The mechanisms underlying the association between SA and carotid atherosclerosis may differ for carotid plaque and carotid intima-media thickness.
| S-EPMC6878193 | biostudies-literature
Project description:ObjectiveP-selectin is a cellular adhesion molecule that has been shown to be crucial in development of coronary heart disease (CHD). We sought to determine the role of P-selectin on the risk of atherosclerosis in a large multi-ethnic population.MethodsData from the Multi-Ethnic Study of Atherosclerosis (MESA), including 1628 African, 702 Chinese, 2393 non-Hispanic white, and 1302 Hispanic Americans, were used to investigate the association of plasma P-selectin with CHD risk factors, coronary artery calcium (CAC), intima-media thickness, and CHD. Regression models were used to investigate the association between P-selectin and risk factors, Tobit model for CAC, and Cox regression for CHD events.ResultsMean levels of P-selectin differed by ethnicity and were higher in men (P<0.001). For all ethnic groups, P-selectin was positively associated with measures of adiposity, blood pressure, current smoking, LDL, and triglycerides and inversely with HDL. A significant ethnic interaction was observed for the association of P-selectin and prevalent diabetes; however, P-selectin was positively associated with HbA1c in all groups. Higher P-selectin levels were associated with greater prevalence of CAC. Over 10.1 years of follow-up, there were 335 incident CHD events. There was a positive linear association between P-selectin levels and rate of incident CHD after adjustment for traditional risk factors. However, association was only significant in non-Hispanic white Americans (HR: 1.81, 95% CI 1.07 to 3.07, P=0.027).ConclusionWe observed ethnic heterogeneity in the association of P-selectin and risk of CHD.
| S-EPMC4397161 | biostudies-literature
Project description:We examined cross-sectional associations between sex hormones and carotid artery intimal-medial thickness (cIMT) and coronary artery calcium in women in the Multi-Ethnic Study of Atherosclerosis. Serum testosterone, estradiol, sex hormone binding globulin (SHBG), and dehydroepiandrosterone levels were measured in 1947 postmenopausal women aged 45-84 years (30% White, 14% Chinese-American, 31% Black, and 25% Hispanic) and not on hormone therapy. Using multiple linear regression we evaluated associations between log(sex hormone) levels and log(cIMT) adjusted for age, ethnicity, body mass index (BMI) and cardiac risk factors. Associations between sex hormone levels and the presence and extent of coronary calcium were evaluated. Total and bioavailable testosterone were positively associated with common cIMT independent of age, BMI, hypertension, smoking, HDL-cholesterol, LDL-cholesterol and insulin sensitivity (p=0.009 and p=0.002, respectively). SHBG was negatively associated with common cIMT (p=0.001) but further adjustment for BMI, cardiovascular risk factors, and LDL- and HDL-cholesterol removed significance. Estradiol and dehydroepiandrosterone were not associated with common cIMT. Sex hormones were not associated with presence of coronary calcium. Among women with measurable coronary calcium, higher SHBG (p=0.012) and lower bioavailable testosterone (p=0.007) were associated with greater coronary calcium score. No heterogeneity by ethnicity was found. In postmenopausal women, testosterone is independently associated with greater common cIMT. SHBG is negatively associated and this may be mediated by LDL- and HDL-cholesterol. In contrast, SHBG and testosterone were associated with extent of coronary calcium but in the opposite direction compared to carotid intimal-medial thickness. These differences warrant further evaluation.
| S-EPMC2729280 | biostudies-literature
Project description:Rationale & objectiveAlthough socioeconomic status has been associated with chronic kidney disease (CKD), little is known about its relationship to residential neighborhood context.Study designSecondary analysis of the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study designed to investigate the development and progression of subclinical cardiovascular disease.Setting & participants6,814 men and women who were between 45 and 84 years of age and free of cardiovascular disease were recruited between 2000 and 2002 from Baltimore, MD; Chicago, IL; Forsyth County, NC; Los Angeles, CA; New York, NY; and St. Paul, MN.ExposuresA composite neighborhood problem score (calculated based on 7 participant-reported domains at study entry: adequacy of food sources, availability of parks/playground, noise, sidewalks, traffic, trash and litter, and violence) and a social cohesion score (calculated based on 5 participant-reported attributes of people in their neighborhood: close knit; get along; willing to help neighbors; trustworthy; and share values).OutcomesEstimated glomerular filtration rate (eGFR; calculated using the CKD-EPI [CKD Epidemiology Collaboration] creatinine-cystatin C equation) and an indicator of eGFR decline > 30% since study entry using follow-up eGFR quantified at 4 examinations: 2000 to 2002, 2004 to 2005, 2005 to 2007, and 2010 to 2011.Analytical approachAssociations between each neighborhood measure (in separate models) and eGFR decline > 30% from baseline and annualized eGFR change were estimated using Cox proportional hazards and linear mixed regression models, respectively, adjusting for potential confounders.ResultsWhile neighborhood social context differs by race/ethnicity, neither neighborhood problems nor social cohesion was independently associated with eGFR decline after adjustment for confounders.LimitationsIncomplete capture of the early stages of eGFR decline, reliance on observational data, limited variation in neighborhood measures, and the potential for residual confounding.ConclusionsAlthough we showed no independent association between neighborhood context and eGFR decline, it is associated with many CKD risk factors and further work is needed to clarify whether it has an independent role in CKD.
| S-EPMC6594400 | biostudies-literature
Project description:ObjectivesExamine the associations of sleep measures with kidney function changes over time among individuals from a community-based study.MethodsThe sample includes 1657 participants (287 with chronic kidney disease [CKD]) in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (mean age: 57.7 years, male: 46.0%). We examined associations between a large set of sleep variables (polysomnography, actigraphy, and questionnaires) and cardiovascular disease risk factors and changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio over approximately 5 years using high-dimensional regression. We investigated the modifying effect of sleep on the associations between cardiovascular disease risk factors and kidney function.ResultsSleep metrics predicted kidney function decline only among individuals with baseline CKD. Among this group, eGFR decline was associated with decreased stage N3 sleep (0.32 mL/min/1.73 m2/y per 10% decrease in N3, p < .001); increased actigraphy napping frequency (beta: -0.20 [-0.30, -0.07]); and actigraphy sleep midpoint trajectory in early morning (ref: midnight, beta: -0.84 [-1.19, -0.50]). Urinary albumin-to-creatinine ratio increase was associated with high wake bouts trajectory (ref: low, beta: 0.97 [0.28, 1.67]) and increased sleep-related hypoxemia (oxygen saturation %time<90 [≥5%], beta: 2.17 [1.26, 3.08]). Sleep metrics--N3 sleep, naps, and midpoint trajectory--significantly modified associations between hemoglobin A1C and eGFR decline.ConclusionsReduced deep sleep, daytime napping, increased wake bouts, delayed sleep rhythms, and overnight hypoxemia are associated with longitudinal kidney function decline, with effects most apparent in individuals with CKD. Deep sleep, napping, and sleep timing modified the association between hemoglobin A1C and kidney function.
| S-EPMC9772248 | biostudies-literature
Project description:Renal artery calcium (RAC) has been shown to be associated with higher odds of hypertension (HTN). The purpose of this study was to determine if the presence and extent of RAC is associated with renal function. We analyzed cross-sectional data from the Multi-Ethnic Study of Atherosclerosis (MESA). A subsample of 1,226 participants underwent computed tomography of the abdomen and also had venous blood samples measured for kidney function. RAC was the primary predictor variable and the following measures of kidney function were the outcome variables: estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and chronic kidney disease (CKD) stage. The analyses were adjusted for age, gender, race, height, visceral fat, dyslipidemia, diabetes, cigarette smoking, hypertension, interleukin-6 and abdominal aortic calcium (AAC). The average age of this cohort was 66.1 years (SD 9.7), 44.8% (549 of 1,226) were men, and nearly 30% had RAC?>0. Compared with those with no RAC, those with RAC?>0 were significantly older but not different by gender or race. After adjustment for age, gender, and race, those with RAC?>0 had significantly higher visceral fat, were more likely to have dyslipidemia, diabetes, and hypertension, had a higher interleukin-6, and a higher prevalence of AAC?>0. The mean eGFR and UACR among those without RAC were 80?ml/min/1.73?m2 and 21?mg/g, whereas these values were 78?ml/min/1.73?m2 and 55?mg/g among those with RAC. In fully adjusted multivariable linear regression models, the presence of RAC was associated with a lower eGFR (??=?-2.21, p?=?0.06) but not with UACR (??=?0.02, p?=?0.79). In fully adjusted ordinal logistic regression, RAC as a continuous variable was associated with increased odds of being in a worse CKD category (odds ratio?1.14, p?=?0.05). When measured by eGFR and CKD stage, there is a modest relation between RAC and kidney function. Further studies might involve clinical trials to assess the role of intensive cardiovascular disease risk factor management in patients with subclinical RAC to determine if this may prevent or delay the development and progression of CKD.
| S-EPMC5614839 | biostudies-literature
Project description:Tissue factor pathway inhibitor (TFPI) is an endothelial membrane-associated anticoagulant protein. Higher circulating levels might reflect endothelial damage.We hypothesized an association of higher total TFPI with subclinical atherosclerosis.Total TFPI was measured in 1000 participants of the Multi-Ethnic Study of Atherosclerosis, a cohort of 6814 men and women without clinical vascular disease, aged 45-84, from four ethnic groups. Subclinical atherosclerosis measures were coronary artery calcium (CAC), carotid intima-media thickness (IMT) and ankle-brachial index (ABI).TFPI was higher with age, male gender, higher LDL-cholesterol, smoking and diabetes, but not ethnicity. Adjusting for risk factors, TFPI in the 4th quartile versus 1st quartile was associated with a 1.2-fold increased risk of detectable CAC (95% CI 1.0-1.4), a 2.1-fold increased risk of CAC >400 Agatston units (95% CI 1.1-4.0) and a 1.6-fold (95% CI 1.1-2.5) increased risk of internal carotid IMT above the 80th percentile, but not with external carotid IMT or low ABI. Findings were consistent across ethnic groups.In this diverse population, higher total TFPI was associated with prevalent CAC (limited to levels >400 units), and elevated internal carotid IMT, independent of other factors. Higher TFPI may indicate endothelial dysfunction. Further study is needed of TFPI and progression of atherosclerosis.
| S-EPMC2784263 | biostudies-literature
Project description:BACKGROUND:Lung fibrosis is attributed to derangements in extracellular matrix remodeling, a process driven by collagen turnover. We examined the association of two collagen biomarkers, carboxy-terminal telopeptide of collagen type I (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP), with subclinical interstitial lung disease (ILD) in adults. METHODS:We performed a cross-sectional analysis of 3244 participants age 45-84 years in the Multi-Ethnic Study of Atherosclerosis. Serum ICTP and PIIINP levels were measured at baseline by radioimmunoassay. Subclinical ILD was defined as high attenuation areas (HAA) in the lung fields on baseline cardiac CT scans. Interstitial lung abnormalities (ILA) were measured in 1082 full-lung CT scans at 9.5 years median follow-up. We used generalized linear models to examine the associations of collagen biomarkers with HAA and ILA. RESULTS:Median (IQR) for ICTP was 3.2??g/L (2.6-3.9??g/L) and for PIIINP was 5.3??g/L (4.5-6.2??g/L). In fully adjusted models, each SD increment in ICTP was associated with a 1.3% increment in HAA (95% CI 0.2-2.4%, p?=?0.02) and each SD increment in PIIINP was associated with a 0.96% increment in HAA (95% CI 0.06-1.9%, p?=?0.04). There was no association between ICTP or PIIINP and ILA. There was no evidence of effect modification by gender, race, smoking status or eGFR. CONCLUSIONS:Higher levels of collagen biomarkers are associated with greater HAA independent of gender, race and smoking status. This suggests that extracellular matrix remodeling may accompany subclinical ILD prior to the onset of clinically evident disease.
| S-EPMC6310068 | biostudies-literature