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1.  Association of Albumin-Creatinine Ratio and Cystatin C With Change in Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Low ankle-brachial index (ABI) is a reflection of atherosclerotic disease, and high ABI is an indicator of calcified vessels. The associations of albuminuria and cystatin C with incidence of either low or high ABI are unknown.
Study Design
Prospective longitudinal cohort study.
Setting & Participants
The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled community-dwelling adults (N=6,814) aged 45–84 years who were free of clinical cardiovascular disease (CVD) at baseline.
Predictors
Baseline albumin-creatinine ratio (ACR) and serum cystatin C levels.
Outcomes
Development of low (< 0.90), and high (> 1.40) ABI using multinomial regression among persons with ABI 0.90–1.40 at baseline.
Results
During 9.8 years of follow up, 221 and 89 participants progressed to low and high ABI, respectively. Baseline ACR and cystatin C were higher among progressors compared to non-progressors. In multivariable analyses, doubling of ACR was associated with increased risk of progression to low (OR, 1.08; 95% CI, 0.99–1.20) and high (OR, 1.16; 95% CI, 1.01–1.32) ABI. Compared to the lowest quintile, the highest quintile of ACR had a significantly increased risk of progression to low (OR, 1.79; 95% CI, 1.03–3.12) and high (OR, 2.76; 95% CI, 1.32–5.77) ABI. Higher cystatin C levels were associated with progression to low (OR per 1-SD greater, 1.12; 95% CI, 1.00–1.26) but not high (OR per 1-SD greater, 1.01; 95% CI, 0.81–1.25) ABI, but the highest quintile of cystatin C was not independently associated with either outcome.
Limitations
Single measure of albuminuria and low number of progressors to high ABI.
Conclusions
In adults free of clinical CVD, albuminuria was a strong, independent risk factor for the development of both high and low ABI, important and different measures of peripheral artery disease.
doi:10.1053/j.ajkd.2014.05.014
PMCID: PMC4272615  PMID: 24998036
Cystatin C; albuminuria; albumin-creatinine ratio (ACR); peripheral artery disease (PAD); ankle-brachial index (ABI); chronic kidney disease (CKD); cardiovascular disease (CVD); atherosclerotic disease
2.  Association of fibroblast growth factor-23 with arterial stiffness in the Multi-Ethnic Study of Atherosclerosis 
Nephrology Dialysis Transplantation  2014;29(11):2099-2105.
Background
Serum fibroblast growth factor-23 (FGF-23) is associated with cardiovascular disease (CVD), yet the mechanisms remain uncertain. Our objective was to determine whether higher FGF-23 concentrations are associated with arterial stiffness.
Methods
In this cross-sectional study, serum FGF-23 concentrations were measured in 5977 participants without known CVD in the Multi-Ethnic Study of Atherosclerosis. The primary outcomes of interest were large (LAE) and small artery elasticity (SAE), pulse pressure and ankle-brachial index (ABI) > 1.30. LAE and SAE were measured by pulse contour analysis of the radial artery. Pulse pressure was measured with an automated sphygmomanometer using the average of two resting blood pressure measurements. ABI was calculated as the ratio of the ankle and brachial systolic blood pressures.
Results
Serum FGF-23 concentrations were not significantly associated with LAE [relative difference (RD) per doubling: 0%; 95% confidence interval (CI): −2–1%], SAE (RD per doubling: 0%; 95% CI: −3–2%), pulse pressure (β per doubling: 0.44; 95% CI: −0.31–1.19), or a high ABI (odds ratio per doubling: 1.14; 95% CI: 0.84–1.55). Findings were similar irrespective of chronic kidney disease status.
Conclusions
Higher serum FGF-23 concentrations are not associated with arterial stiffness, as measured by pulse pressure, LAE, SAE or high ABI, in a community-based population without CVD.
doi:10.1093/ndt/gfu101
PMCID: PMC4209876  PMID: 24782533
ABI; arterial elasticity; arterial stiffness; FGF-23; pulse pressure
3.  Risk Factors for Cardiovascular Disease across the Spectrum of Older Age: The Cardiovascular Health Study 
Atherosclerosis  2014;237(1):336-342.
Objective
The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.
Methods
Participants (n=4,883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65–74, 75–84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).
Results
There were 1,498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65–74, 75–84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65–74, 75–84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).
Conclusions
The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.
doi:10.1016/j.atherosclerosis.2014.09.012
PMCID: PMC4254262  PMID: 25303772
aging; epidemiology; risk factors
4.  Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness 
PLoS ONE  2015;10(10):e0141251.
Background
Endothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS.
Methods
We studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers.
Results
Higher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes.
Conclusions
In critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.
doi:10.1371/journal.pone.0141251
PMCID: PMC4619633  PMID: 26492036
5.  Low Serum Bicarbonate and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate concentrations with early declines in kidney function is less clear.
Study Design
Retrospective cohort study.
Setting & Participants
6380 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/1.73m2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine–cystatin C equation.
Predictors
Serum bicarbonate concentrations.
Outcomes
Rapid kidney function decline (eGFR decline >5% per year) and incident reduced eGFR (eGFR<60 mL/min/1.73 m2 with minimum rate of eGFR loss of 1 mL/min/1.73 m2 per year).
Results
The average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%–20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03–1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate <21mEq/L relative to 23–24 mEq/L was 1.35 (95% CI, 1.05–1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83–1.62) for incident reduced eGFR.
Limitations
Etiology of metabolic acidosis cannot be determined in this study.
Conclusions
Lower serum bicarbonate concentrations are independently associated with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with a baseline eGFR >60 mL/min/1.73 m2. If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria, or may have a causal role in the development of an eGFR <60 mL/min/1.73 m2.
doi:10.1053/j.ajkd.2014.05.008
PMCID: PMC4177290  PMID: 24953891
serum bicarbonate; metabolic acidosis; chronic kidney disease (CKD); kidney function; renal disease; disease progression; kidney disease trajectory
6.  Systolic and Diastolic Blood Pressure, Incident Cardiovascular Events and Death in Elderly Persons: The Role of Functional Limitation in the Cardiovascular Health Study 
Hypertension  2014;64(3):472-480.
Whether limitation in ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic (SBP) and diastolic (DBP) blood pressure with cardiovascular events (CVD) and death differs is unclear.
We evaluated whether limitation in ADL or gait speed modify the association of SBP or DBP with incident CVD (N= 2,358) and death (N=3,547) in the Cardiovascular Health Study.
Mean age was 78 ± 5 and 21% reported limitation in ≥1 ADL. There were 778 CV events and 1,289 deaths over 9 years. Among persons without and with ADL limitation, SBP was associated with incident CVD: HR (per 10 mmHg increase) 1.08 (95% CI 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP > 80, compared with <65 mmHg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66–80 mmHg and HR 0.49 (0.25, 0.94) for DBP > 80, compared to DBP ≤ 65. Among persons with ADL limitation, a DBP 66–80 had the lowest risk for death, HR 0.72 (0.57, 0.91), compared with DBP ≤ 65. Associations did not vary by 15 feet walking speed
ADL can identify elders in whom diastolic hypotension is associated with higher CV risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders.
doi:10.1161/HYPERTENSIONAHA.114.03831
PMCID: PMC4134400  PMID: 24935945
hypertension; elderly; functional status; cardiovascular
7.  Fibroblast Growth Factor-23 and Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) 
Circulation  2014;130(4):298-307.
Background
Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.
Methods and Results
We tested associations of circulating FGF-23 concentration with incident AF among 6,398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1,350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over 7.7 and 8.0 years median follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each two-fold higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (HR 1.41 [95% CI 1.13-1.76], p=0.003) and a 30% higher risk of incident AF in CHS (HR 1.30 [95% CI 1.05-1.61], p=0.016), adjusting for potential confounding characteristics including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (HR 1.15 per 0.5 mg/dL [CI 1.02-1.31], p-value=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjusting for FGF-23.
Conclusions
Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.
doi:10.1161/CIRCULATIONAHA.113.005499
PMCID: PMC4108550  PMID: 24920722
atrial fibrillation; fibroblast growth factor; mineral; chronic kidney disease
8.  Sex differences in the prevalence and clinical outcomes of subclinical peripheral artery disease in the Health, Aging, and Body Composition (Health ABC) study 
Vascular  2013;22(2):142-148.
The objective of the study was to determine if there are sex-based differences in the prevalence and clinical outcomes of subclinical peripheral artery disease (PAD). We evaluated the sex-specific associations of ankle–brachial index (ABI) with clinical cardiovascular disease outcomes in 2797 participants without prevalent clinical PAD and with a baseline ABI measurement in the Health, Aging, and Body Composition study. The mean age was 74 years, 40% were black, and 52% were women. Median follow-up was 9.37 years. Women had a similar prevalence of ABI < 0.9 (12% women versus 11% men; P=0.44), but a higher prevalence of ABI 0.9–1.0 (15% versus 10%, respectively; P < 0.001). In a fully adjusted model, ABI < 0,9 was significantly associated with higher coronary heart disease (CHD) mortality, incident clinical PAD and incident myocardial infarction in both women and men. ABI < 0.9 was significantly associated with incident stroke only in women. ABI 0.9–1.0 was significantly associated with CHD death in both women (hazard ratio 4.84, 1.53–15.31) and men (3.49, 1.39–8.721. However, ABI 0.9–1.0 was significantly associated with incident clinical PAD (3.33, 1.44–7.70) and incident stroke (2.45, 1.38–4.35) only in women. Subclinical PAD was strongly associated with adverse CV events in both women and men, but women had a higher prevalence of subclinical PAD.
doi:10.1177/1708538113476023
PMCID: PMC4509626  PMID: 23512905
women; sex-specific; peripheral artery disease; epidemiology
9.  Kidney Function and Cognitive Health in Older Adults: The Cardiovascular Health Study 
American Journal of Epidemiology  2014;180(1):68-75.
Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C–based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m2 had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m2. Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m2 had fewer cognitive impairment–free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m2, independent of confounders and mediating cardiovascular events (mean difference = −0.44, 95% confidence interval: −0.62, −0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function.
doi:10.1093/aje/kwu102
PMCID: PMC4070934  PMID: 24844846
aging; chronic kidney disease; cognitive function; congestive heart failure; myocardial infarction; prospective study; stroke; successful aging
10.  Urinary Kidney Injury Molecule 1 (KIM-1) and Interleukin 18 (IL-18) as Risk Markers for Heart Failure in Older Adults: The Health, Aging, and Body Composition (Health ABC) Study 
Background
Kidney damage and reduced kidney function are potent risk factors for heart failure (HF), but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of HF.
Study Design
Retrospective cohort study.
Setting & Participants
2921 participants without HF in the Health, Aging, and Body Composition (Health ABC) cohort.
Predictors
Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively).
Outcomes
Incident HF over a median follow-up of 12 years.
Results
Median values of each marker at baseline were 812 (IQR, 497–1235) pg/mg for KIM-1:Cr, 31 (IQR, 19–56) pg/mg for IL-18:Cr, and 8 (IQR, 5–19) mg/g for ACR. 596 persons developed HF during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident HF after adjustment for baseline eGFR, HF risk factors, and ACR (HR, 1.32; 95% CI, 1.02–1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr was also associated with HF in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05–1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89–1.48). The top quartile of ACR had a stronger adjusted association with HF (HR, 1.96; 95% CI, 1.53–2.51).
Limitations
Generalizability to other populations is uncertain.
Conclusions
Higher urine concentrations of KIM-1 were independently associated with incident HF risk, although the associations of higher ACR were of stronger magnitude.
doi:10.1053/j.ajkd.2014.01.432
PMCID: PMC4069223  PMID: 24656453
IL-18; KIM-1; cystatin C; heart failure; CKD; risk marker; cardiovascular disease (CVD); albuminuria; kidney tubular injury
11.  Dietary Protein Intake and Change in Estimated GFR in the Cardiovascular Health Study 
Objective
With aging, kidney function declines, as evidenced by reduced glomerular filtration rate. It is controversial whether or not high protein intake accelerates the kidney function decline.
Research Methods & Procedures
We examined whether dietary protein is associated with change in kidney function (mean follow-up 6.4 (SD=1.4, range = 2.5 to 7.9) years in the Cardiovascular Health Study (n =3,623). We estimated protein intake using a food frequency questionnaire (FFQ) and estimated glomerular filtration rate (eGFR) from cystatin C. Associations between protein intake and kidney function were determined by linear and logistic regression models.
Results
Average protein intake was 19% of energy intake (SD=5%). Twenty-seven percent (n=963) of study participants had rapid decline in kidney function, as defined by (ΔeGFRcysC > 3 mL/min per 1.73 m2). Protein intake (characterized as g/day and % energy/day), was not associated with change in eGFR (P>0.05 for all comparisons). There were also no significant associations when protein intake was separated by source (animal and vegetable).
Conclusion
These data suggest that higher protein intake does not have a major impact on kidney function decline among elderly men and women.
doi:10.1016/j.nut.2013.12.006
PMCID: PMC4082792  PMID: 24984995
kidney; glomerular filtration rate; vegetable protein; animal protein; macronutrients
12.  Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans 
JAMA  2014;312(20):2115-2125.
IMPORTANCE
The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain.
OBJECTIVE
To describe the relationship between SCT and CKD and albuminuria in self-identified African Americans.
DESIGN, SETTING, AND PARTICIPANTS
Using 5 large, prospective, US population-based studies (the Atherosclerosis Risk in Communities Study [ARIC, 1987–2013; n = 3402], Jackson Heart Study [JHS, 2000–2012; n = 2105], Coronary Artery Risk Development in Young Adults [CARDIA, 1985–2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA, 2000–2012; n = 1620], and Women’s Health Initiative [WHI, 1993–2012; n = 8000]), we evaluated 15 975 self-identified African Americans (1248 participants with SCT [SCT carriers] and 14 727 participants without SCT [noncarriers]).
MAIN OUTCOMES AND MEASURES
Primary outcomes were CKD (defined as an estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 at baseline or follow-up), incident CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of >30 mg/g or albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately for each cohort and were subsequently meta-analyzed using a random-effects model.
RESULTS
A total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of 14 722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs 1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers [19.6%]) had albuminuria during the study period. Individuals with SCT had an increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34–1.84]; absolute risk difference [ARD], 7.6% [95% CI, 4.7%–10.8%]), incident CKD (OR, 1.79 [95% CI, 1.45–2.20]; ARD, 8.5% [95% CI, 5.1%–12.3%]), and decline in eGFR (OR, 1.32 [95% CI, 1.07–1.61]; ARD, 6.1% [95% CI, 1.4%–13.0%]) compared with noncarriers. Sickle cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49–2.31]; ARD, 12.6% [95% CI, 7.7%–17.7%]).
CONCLUSIONS AND RELEVANCE
Among African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These findings suggest that SCT may be associated with the higher risk of kidney disease in African Americans.
doi:10.1001/jama.2014.15063
PMCID: PMC4356116  PMID: 25393378
13.  The Interaction of Age with Lipoproteins as Predictors of Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis 
Archives of internal medicine  2008;168(11):1200-1207.
Background
Previous epidemiologic studies have shown that low-density lipoprotein is an independent risk factor for prevalent aortic valve calcification (AVC); however, to our knowledge, the interactions between plasma lipoprotein concentrations and age on the relative risks (RRs) for AVC prevalence and severity have not been examined in a large, racially and ethnically diverse cohort.
Methods
Using stepwise RR regression, the relationships of baseline fasting lipid levels and lipoprotein levels to baseline prevalence and severity of AVC were determined in 5801 non–statin-using participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
Results
In age-stratified, adjusted analyses, the low-density lipoprotein–associated RRs (95%confidence intervals) for prevalent AVC were higher for younger compared with older participants (age 45-54 years, 1.69 [1.19-2.39]; age 55-64 years, 1.48 [1.24-1.76]; age 65-74 years, 1.09 [0.95-1.25]; and age 75-84 years, 1.16 [0.99-1.36]; P interaction=.04]. There was a similar, significant interaction of age with total cholesterol–associated RR for prevalent AVC (P interaction=.04). In contrast, total- to high-density lipoprotein cholesterol ratio RRs were similar across all age strata (P interaction=.68). At multivariate analyses, no lipoprotein parameter was associated with AVC severity.
Conclusions
In this racially and ethnically diverse, preclinical cohort, low-density lipoprotein was a risk factor for AVC only in participants younger than 65 years, whereas the total cholesterol/high-density lipoprotein cholesterol ratio was associated with a modest increased risk of AVC across all ages. These findings may have important implications for the efficacy of and targets for dyslipidemia therapies in calcific aortic valve disease.
doi:10.1001/archinte.168.11.1200
PMCID: PMC4441013  PMID: 18541828
14.  Ethnic and Gender Differences in Liver Fat on Cardiac Computed Tomography: The Multi-Ethnic Study of Atherosclerosis 
Mayo Clinic proceedings  2014;89(4):493-503.
Objective
To describe ethnic and gender differences in the prevalence and determinants of fatty liver in a multi-ethnic cohort.
Patients and Methods
We studied participants from the Multi-Ethnic Study of Atherosclerosis who underwent baseline non-contrast cardiac CT between July 2000-August 2002, and had adequate hepatic and splenic imaging for fatty liver determination (n=4088). Fatty liver was diagnosed by a liver/spleen attenuation ratio <1. We compared the prevalence and severity of fatty liver, among four ethnicities (White, Chinese, African American, Hispanic), stratifying by obesity and metabolic syndrome. Multivariable ordinal logistic regression was employed to determine the impact of cardio-metabolic risk factors on fatty liver prevalence in different ethnicities.
Results
The prevalence of fatty liver varied significantly by ethnicity (White 15%, Chinese 20%, African-American 11%, Hispanic 27%, p<0.001). Although African-Americans had the highest prevalence of obesity, a smaller percentage of obese African Americans were diagnosed with fatty liver compared to other ethnicities (African American 17%, White 31%, Chinese 37%, Hispanic 39%, p<0.001). Hispanics demonstrated the highest prevalence of fatty liver, including among the obese and metabolic syndrome population. An increase in insulin resistance predicted a two-fold increased prevalence of fatty liver in all ethnicities after multi-variable adjustment.
Conclusion
African-Americans have a lower prevalence, and Hispanic Americans a higher prevalence of fatty liver compared to other ethnicities. There are distinct ethnic variations in the prevalence of fatty liver even among patients with the metabolic syndrome or obesity, suggesting that genetic factors may play a significant role in the phenotypic expression of fatty liver.
doi:10.1016/j.mayocp.2013.12.015
PMCID: PMC4410019  PMID: 24613289
Non-alcoholic Fatty Liver Disease; Ethnicity; Computed Tomography
15.  Serum Phosphate is Associated with Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2014;233(2):331-337.
Objectives
This study sought to investigate associations of phosphate metabolism biomarkers with aortic valve calcification (AVC).
Background
Calcific aortic valve disease (CAVD) is a common progressive condition that involves inflammatory and calcification mediators. Currently there are no effective medical treatments, but mineral metabolism pathways may be important in the development and progression of disease.
Methods
We examined associations of phosphate metabolism biomarkers, including serum phosphate, urine phosphate, parathyroid hormone (PTH) and serum fibroblast growth factor (FGF)-23, with CT-assessed AVC at study baseline and in short-term follow-up in 6,814 participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
Results
At baseline, AVC prevalence was 13.2%. Higher serum phosphate levels were associated with significantly greater AVC prevalence (relative risk 1.3 per 1mg/dL increment, 95% confidence incidence: 1.1 to 1.5, p < 0.001). Serum FGF-23, serum PTH, and urine phosphate were not associated with prevalent AVC. Average follow-up CT evaluation was 2.4 years (range 0.9–4.9 years) with an AVC incidence of 4.1%. Overall, phosphate metabolism biomarkers were not associated with incident AVC except in the top FGF-23 quartile.
Conclusions
Serum phosphate levels are significantly associated with AVC prevalence. Further study of phosphate metabolism as a modifiable risk factor for AVC is warranted.
doi:10.1016/j.atherosclerosis.2013.12.051
PMCID: PMC3992246  PMID: 24530958
Phosphate; Aortic Valve; Calcification
16.  Relative risks of Chronic Kidney Disease for mortality and End Stage Renal Disease across races is similar 
Kidney international  2014;86(4):819-827.
Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% whites, and 4% blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, whites, and blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45-59 vs. 90-104 ml/min/1.73m2 were 1.3 (1.2-1.3), 1.1 (1.0-1.2) and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding HRs for ACR 30-299 mg/g or dipstick 1+ compared with ACR <10 or dipstick negative were 1.61 (1.41-1.84), 1.7 (1.5-1.9) and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races.
doi:10.1038/ki.2013.553
PMCID: PMC4048178  PMID: 24522492
17.  Relative risks of Chronic Kidney Disease for mortality and End Stage Renal Disease across races is similar 
Kidney international  2014;86(4):819-827.
Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% whites, and 4% blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, whites, and blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45–59 vs. 90–104 ml/min/1.73m2 were 1.3 (1.2–1.3), 1.1 (1.0–1.2) and 1.3 (1.1–1.7) for all-cause mortality, 1.6 (1.5–1.8), 1.4 (1.2–1.7), and 1.4 (0.7–2.9) for cardiovascular mortality, and 27.6 (11.1–68.7), 11.2 (6.0–20.9), and 4.1 (2.2–7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30–299 mg/g or dipstick 1-positive vs. an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4–1.8), 1.7 (1.5–1.9) and 1.8 (1.7–2.1) for all-cause mortality, 1.7 (1.4–2.0), 1.8 (1.5–2.1), and 2.8 (2.2–3.6) for cardiovascular mortality, and 7.4 (2.0–27.6), 4.0 (2.8–5.9), and 5.6 (3.4–9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races.
doi:10.1038/ki.2013.553
PMCID: PMC4048178  PMID: 24522492
18.  Fibroblast Growth Factor 23, the Ankle-Brachial Index, and Incident Peripheral Artery Disease in the Cardiovascular Health Study 
Atherosclerosis  2014;233(1):91-96.
Background
Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.
Methods
Using data (N=3,143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults > 65 years of age, we analyzed the cross sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.
Results
The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1–1.4, FGF23 at baseline was associated with prevalent PAD (ABI<0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76–1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75–1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28–3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79–2.70).
Conclusions
In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.
doi:10.1016/j.atherosclerosis.2013.12.015
PMCID: PMC3927151  PMID: 24529128
Fibroblast growth factor; peripheral artery disease; ankle-brachial index; chronic kidney disease; cardiovascular disease
19.  Association between inflammatory markers and liver fat: The Multi-Ethnic Study of Atherosclerosis 
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is a common liver disease. Data is emerging that an independent association between markers of subclinical atherosclerosis and NAFLD exists and it may be considered as an independent predictor of cardiovascular (CV) outcomes. We aim to better characterize the relationship between NAFLD and inflammatory markers in a multi-ethnic cohort by assessing fatty liver on computed tomography (CT) scans.
METHODS
The Multi-Ethnic Study of Atherosclerosis (MESA) is a longitudinal, population-based study from four ethnic groups free of CV disease at baseline. The inflammatory markers studied include: C-reactive protein (CRP) and interleukin 6 (IL-6). On CT scans liver-to-spleen ratio (LSR: Hounsfield Units (HU) of the liver divided by HU of spleen) of <1 and liver attenuation of <40 HU were used as criteria for fatty liver. Unadjusted and adjusted multivariate linear and logistic regression analysis was performed.
RESULTS
4038 participants amongst 6814 MESA population with visible spleen on the CT scan, available CRP and IL-6 levels and no reported liver cirrhosis were included. The average age was 61 +/− 10 years, 37% Caucasians and 45% were males. Mean CRP and IL-6 were 2.36 mg/dl and 1.37 pg/ml respectively. 696 participants (17%) had LSR of <1 and 253 (6%) had liver attenuation of <40 HU. When using LSR <1 as a continuous variable, the correlation (adjusted odds ratio (OR)) with CRP >2.0 was 0.037 (95% CI: 0.02-0.054) and with IL-6 was 0.014 (95% CI: 0.004-0.023). On the other hand when presence and absence of LSR <1 was considered, higher ORs for association with CRP >2: 1.41 (95% CI: 1.16 to 1.73) and IL6:1.18 (95% CI: 1.05 to 1.31) were found. Similarly, the adjusted association of per unit decrease in liver attenuation with CRP>2 was 1.92 (95% CI: 1.20 to 2.63) while for IL-6 was 1.08 (95% CI: 0.69 to 1.47). When considering presence and absence of liver attenuation <40 HU the OR for CRP >2 was 2.27 (95% CI: 1.62 to 3.16) and for IL-6 was 1.33 (95% CI: 1.13 to 1.58).
CONCLUSION
CRP and IL-6 levels were found to be significantly associated with liver fat assessed on CT scan after adjusting for other risk factors for atherosclerosis.
doi:10.4172/2155-9880.1000344
PMCID: PMC4296580  PMID: 25598995
Inflammation; Non-alcoholic fatty liver disease; computed tomography scan; C reactive protein
20.  Association of a Cystatin C Gene Variant With Cystatin C Levels, CKD, and Risk of Incident Cardiovascular Disease and Mortality 
Background
Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFRcys). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of CKD, and strengthen risk estimates for cardiovascular disease (CVD) and mortality.
Study Design
Observational.
Setting & Population
Four population-based cohorts: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health, Aging, and Body Compostion (Health ABC) studies.
Predictors
We estimated the association of rs13038305 with eGFRcys and eGFRcr, and performed longitudinal analyses of the associations of eGFRcys with mortality and cardiovascular events following adjustment for rs13038305.
Outcomes
We assessed reclassification by genotype-adjusted eGFRcys across CKD categories: <45, 45–59, 60–89, and ≥90 mL/min/1.73 m2. We compared mortality and CVD outcomes in those reclassified to a worse eGFRcys category with those unaffected. Results were combined using fixed-effect inverse-variance meta-analysis.
Results
In 14,645 participants, each copy of the T allele of rs13038305 (frequency, 21%), was associated with 6.4% lower cystatin C concentration, 5.5 mL/min/1.73 m2 higher eGFRcys, and 36% [95% CI, 29%–41%] lower odds of CKD. Associations with CVD (HR, 1.17; 95% CI, 1.14–1.20) and mortality (HR, 1.22; 95% CI, 1.19–1.24) per 10- ml/min/1.73 m2 lower eGFRcys were similar with or without rs13038305 adjustment. In total, 1134 participants (7.7%) were reclassified to a worse CKD category following rs13038305 adjustment, and rates of CVD and mortality were higher in individuals who were reclassified. However, the overall net reclassification index was not significant for either outcome, at 0.009 (95% CI, −0.003 to 0.022) for mortality and 0.014 (95% CI, 0.0 to 0.028) for CVD.
Limitations
rs13038305 only explains a small proportion of cystatin C variation.
Conclusions
Statistical adjustment can correct a genetic bias in GFR estimates based on cystatin C in carriers of the T allele of rs13038305 and result in changes in disease classification. However, on a population level, the effects on overall reclassification of CKD status are modest.
doi:10.1053/j.ajkd.2013.06.015
PMCID: PMC3872167  PMID: 23932088
Cystatin C; chronic kidney disease; genetics; single nucleotide polymorphism; net reclassification improvement
21.  Relation of Thoracic Aortic Distensibility to Left Ventricular Area (From the Multi-ethnic Study of Atherosclerosis [MESA]) 
The American journal of cardiology  2013;113(1):178-182.
Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with left ventricular (LV) area on computed tomography (CT), a marker of LV remodeling, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness is independently associated with increased LV area. The study population consisted of 3,540 (61±10 years, 46% men) from the MESA study who underwent aortic distensibility (AD) assessment on magnetic resonance imaging (MRI) and LV area measurement on CT (adjusted to body surface area). Multivariable logistic regression was performed to assess the association between body surface area (BSA) normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical and imaging covariates. The mean LV area /BSA was 2,153 cm2 and mean AD was 1.84 mm Hg−1 x103. Subjects in the lowest AD quartile were older with higher prevalence of hypertension, diabetes, and hypercholesterolemia (p<0.05 for all comparisons). Using multivariate linear regression adjusting for demographics, traditional risk factors, coronary artery calcium and C-reactive protein, each standard deviation decrease was associated with 18 cm2 increase in the LV area. In addition, decreasing AD quartiles were independently associated with increased BSA LV area defined as >75th percentile. In this multi-ethnic cohort, reduced AD was associated with increased LV area. Longitudinal studies are needed to determine if decreased distensibility precedes and directly influences increased LV area.
doi:10.1016/j.amjcard.2013.09.039
PMCID: PMC3912190  PMID: 24210674
Arterial compliance; Left ventricular area; Computed tomography; Aortic Distensibility
22.  Thoracic Aortic Distensibility and Thoracic Aortic Calcium (From the Multi-ethnic Study of Atherosclerosis [MESA]) 
The American journal of cardiology  2010;106(4):575-580.
Decreased arterial distensibility is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with thoracic aortic calcium (TAC), a marker of atherosclerosis, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness is independently associated with increased TAC. We included 3,540 (61±10 years, 46% males) subjects from the Multi-ethnic Study of Atherosclerosis (MESA) study who underwent aortic distensibility (AD) assessment on MRI. TAC was calculated using modified Agatston algorithm on non-contrast cardiac CT. Multivariate regression models were calculated for the presence of TAC. Overall, 861 (24%) individuals had detectable TAC. A lower AD was observed among those with vs. without TAC (2.02±1.34 vs. 1.28±0.74, p<0.0001). The prevalence of TAC increased significantly across decreasing quartiles of AD (7%, 17%, 31%, and 42%, p<0.0001). Using multivariate analysis, TAC was independently associated with AD after adjusting for age, gender, ethnicity and other covariates. In conclusion, our analysis demonstrates that increased arterial stiffness is associated with increased TAC independent of ethnicity and other atherosclerotic risk factors.
doi:10.1016/j.amjcard.2010.03.074
PMCID: PMC4228943  PMID: 20691319
23.  Fibroblast Growth Factor 23, Left Ventricular Mass, and Left Ventricular Hypertrophy in Community-Dwelling Older Adults 
Atherosclerosis  2013;231(1):10.1016/j.atherosclerosis.2013.09.002.
Objectives
In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain.
Methods
C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals ≥65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH.
Results
Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β=6.71 [95% CI 4.35–9.01] g per doubling of FGF23). 32% (n=624) had CKD (eGFR <60 mL/min/1.73m2 and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β=9.71 [95% CI 5.86–13.56] g per doubling of FGF23 compared to those without CKD (β=3.44 [95% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20–1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95% CI 0.97–1.48]).
Conclusion
In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD.
doi:10.1016/j.atherosclerosis.2013.09.002
PMCID: PMC3840534  PMID: 24125420
Left ventricular mass; left ventricular hypertrophy; chronic kidney disease; fibroblast growth factor 23; older adults; cardiovascular disease
24.  Influence of Urine Creatinine Concentrations on the Relation of Albumin-Creatinine Ratio With Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Higher urine albumin-creatinine ratio (ACR) is associated with cardiovascular disease (CVD) events, an association that is stronger than that between spot urine albumin on its own and CVD. Urine creatinine is correlated with muscle mass, and low muscle mass is also associated with CVD. Whether low urine creatinine in the denominator of the ACR contributes to the association of ACR with CVD is uncertain.
Study Design
Prospective cohort study.
Setting & Participants
6,770 community-living individuals without CVD.
Predictors
Spot urine albumin, the reciprocal of the urine creatinine concentration (1/UCr), and ACR.
Outcome
Incident CVD events.
Results
During a mean of 7.1 years’ follow-up, 281 CVD events occurred. Geometric means for spot urine creatinine, urine albumin and ACR were 95 ± 2 (SD) mg/dl, 0.7 ± 3.7 mg/dl and 7.0 ± 3.1 mg/g. Adjusted HRs per 2-fold higher increment in each urinary measures with CVD events were similar (1/UCr: 1.07 [95% CI, 0.94-1.22]; urine albumin: 1.08 [95% CI, 1.01-1.14]; and ACR: 1.11 [95% CI, 1.04-1.18]). Urine creatinine was lower in older, female, and low weight individuals. ACR ≥10 mg/g was more strongly associated with CVD events in individuals with low weight (HR for lowest vs. highest tertile: 4.34 vs. 1.97; p for interaction=0.006). Low weight also modified the association of urine albumin with CVD (p for interaction=0.06), but 1/urine creatinine did not (p for interaction=0.9).
Limitations
We lacked 24-hour urine data.
Conclusions
While ACR is more strongly associated with CVD events among persons with low body weight, this association is not driven by differences in spot urine creatinine. Overall, the associations of ACR with CVD events appear to be driven primarily by urine albumin and less by urine creatinine.
doi:10.1053/j.ajkd.2013.05.010
PMCID: PMC3783582  PMID: 23830183
25.  Association of Obesity and Kidney Function Decline among Non-Diabetic Adults with eGFR > 60 ml/min/1.73m2: Results from the Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Obesity is associated with higher end-stage renal disease incidence, but associations with earlier forms of kidney disease remain incompletely characterized.
Methods
We studied the association of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with rapid kidney function decline and incident chronic kidney disease in 4573 non-diabetic adults with eGFR ≥ 60 ml/min/1.73m2 at baseline from longitudinal Multi-Ethnic Study of Atherosclerosis cohort. Kidney function was estimated by creatinine and cystatin C. Multivariate analysis was adjusted for age, race, baseline eGFR, and hypertension.
Results
Mean age was 60 years old, BMI 28 kg/m2, baseline eGFRCr 82 and eGFRCys 95 ml/min/1.73m2. Over 5 years of follow up, 25% experienced rapid decline in renal function by eGFRCr and 22% by eGFRCys. Incident chronic kidney disease (CKD) developed in 3.3% by eGFRCys, 11% by eGFRCr, and 2.4% by both makers. Compared to persons with BMI < 25, overweight (BMI 25 – 30) persons had the lowest risk of rapid decline by eGFRCr (0.84, 0.71 – 0.99). In contrast, higher BMI categories were associated with stepwise higher odds of rapid decline by eGFRCys, but remained significant only when BMI ≥ 35 kg/m2 (1.87, 1.41 – 2.48). Associations of BMI with incident CKD were insignificant after adjustment. Large WC and WHR were associated with increased risk of rapid decline only by eGFRCys, and of incident CKD only when defined by both filtration markers.
Conclusions
Obesity may be a risk factor for kidney function decline, but associations vary by filtration marker used.
PMCID: PMC4157691  PMID: 25210651
Kidney Function Decline; MESA; Obesity; Waist Circumference; Waist-to-Hip Ratio

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