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ABSTRACT: : Hypertension guidelines recommend screening for chronic kidney disease (CKD) using serum creatinine and urine dipstick; this strategy may lead to misclassification. Persons with occult CKD [i.e. missed by creatinine but detected by cystatin C or albumin-to-creatinine ratio (ACR)] have higher risks for death, cardiovascular events, and end-stage renal disease.
: We studied occult CKD prevalence among nondiabetic, hypertensive adults in National Health and Nutrition Examination Survey 1988-1994 (N = 2088) and 1999-2002 (N = 737). We defined occult CKD as estimated glomerular filtration rate by cystatin C (eGFRcys) less than 60 ml/min per 1.73 m and/or ACR at least 30 mg/g among persons with eGFRcreat more than 60 ml/min per 1.73 m. We studied occult CKD prevalence by either marker, stratified by age, race/ethnicity, and assessed clinical predictors associated with occult CKD presence.
: In 1988-1994, occult CKD was prevalent among 25% of nondiabetic hypertensive persons, and it was 22% in 1999-2002. Each marker's ability to detect occult CKD varied by age and race. Cystatin C detected occult CKD among 8.9% of persons more than 65 years, and among 3.8% of whites. ACR detected occult CKD among 9.3% of persons less than 45 years, 16.6% of Blacks, and 20.6% of Mexican-Americans. In multivariate models, each decade of advancing age was associated with a higher occult CKD prevalence by cystatin C (OR 3.1, 95% CI 2.5-3.8) in 1988-1994 and 1999-2002 (OR 2.9, 1.8-4.6).
: Current hypertension guidelines may fail to detect a large proportion of high-risk individuals with CKD who can be identified by cystatin C or ACR. Future studies are needed to evaluate targeted use of multimarker renal panels among hypertensives.
Journal of hypertension 06/2013; 31(6):1196-202. · 4.02 Impact Factor
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Rajnish Mehrotra, Carmen A Peralta,
Shu-Cheng Chen,
Suying Li,
Michael Sachs,
Anuja Shah,
Keith Norris,
Georges Saab,
Adam Whaley-Connell,
Bryan Kestenbaum,
Peter A McCullough
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ABSTRACT: Whether higher serum phosphorus levels are associated with a higher risk for death and/or progression of chronic kidney disease (CKD) is not well established, and whether the association is confounded by access and barriers to care is unknown. To answer these questions, data of 10,672 individuals identified to have CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) from those participating in a community-based screening program were analyzed. Over a median follow-up of 2.3 years, there was no association between quartiles of serum phosphorus and all-cause mortality (adjusted hazards ratio for serum phosphorus over 3.3 to 3.7, over 3.7 to 4.1, and over 4.1 mg/dl, respectively: 1.22 (0.95-1.56), 1.00 (0.76-1.32), and 1.00 (0.75-1.33); reference, serum phosphorus of 3.3 mg/dl and below). Individuals in the highest quartile for serum phosphorus had a significantly higher risk for progression to end-stage renal disease (ESRD) (unadjusted hazards ratio, 6.72 (4.16-10.85)); however, the risk became nonsignificant on adjustment for potential confounders. There was no appreciable change in hazards ratio with inclusion of variables related to access and barriers to care. Additional analyses in subgroups based on 12 different variables yielded similar negative associations. Thus, in the largest cohort of individuals with early-stage CKD to date, we could not validate an independent association of serum phosphorus with risk for death or progression to ESRD.Kidney International advance online publication, 24 April 2013; doi:10.1038/ki.2013.145.
Kidney International 04/2013; · 6.61 Impact Factor
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Carmen A Peralta,
Eric Vittinghoff,
Nisha Bansal,
David Jacobs,
Paul Muntner,
Bryan Kestenbaum,
Cora Lewis,
David Siscovick,
Holly Kramer,
Michael Shlipak,
Kirsten Bibbins-Domingo
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ABSTRACT: BACKGROUND: Strong racial discrepancies in end-stage renal disease exist. Whether there are race differences in kidney function loss in younger healthy persons is not well established. STUDY DESIGN: Longitudinal. SETTING & PARTICIPANTS: 3,348 black and white adults with at least 2 measurements of cystatin C-based estimated glomerular filtration rate (eGFRcys) at scheduled Coronary Artery Risk Development in Young Adults (CARDIA) examinations (years 10, 15, and 20). PREDICTOR: Race. OUTCOMES & MEASUREMENTS: We used linear mixed models to examine race differences in annualized rates of eGFRcys decline, adjusting for age, sex, lifetime exposure to systolic blood pressure >120 mm Hg, diabetes, and albumin-creatinine ratio. We used Poisson regression to compare racial differences in rapid decline (eGFRcys decline >3% per year) by study period (10-15 years after baseline examination [defining period 1] and >15-20 years after baseline examination [defining period 2]). RESULTS: Mean age was 35 ± 3.6 (SD) years, and mean eGFRcys was 110 ± 20 mL/min/1.73 m2 for blacks and 104 ± 17 mL/min/1.73 m2 for whites at baseline. For both blacks and whites, eGFRcys decline was minimal at younger ages (<35 years) and eGFRcys loss accelerated at older ages. However, acceleration of eGFRcys decline occurred at earlier ages for blacks than whites. Blacks had somewhat faster annualized rates of decline compared with whites, but differences were attenuated after adjustment in period 1 (0.13 mL/min/1.73 m2 per year faster; P = 0.2). In contrast, during period 2, blacks had significantly faster annualized rates of decline, even after adjustment (0.32 mL/min/1.73 m2 per year faster; P = 0.003). The prevalence of rapid decline was significantly higher for blacks versus whites, with prevalence rate ratios of 1.31 (95% CI, 1.04-1.63) for period 1 and 1.24 (95% CI, 1.09-1.41) for period 2. Differences were attenuated after full adjustment: adjusted prevalence rate ratios were 1.20 (95% CI, 0.95-1.49) for period 1 and 1.10 (95% CI, 0.96-1.26) for period 2. LIMITATIONS: No measured GFR. CONCLUSIONS: eGFRcys decline differs by race at early ages, with faster annualized rates of decline for blacks. Future studies are required to explain the observed differences.
American Journal of Kidney Diseases 03/2013; · 5.43 Impact Factor
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JAMA internal medicine. 02/2013; 173(4):325-6.
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ABSTRACT: OBJECTIVE: High circulating concentrations of parathyroid hormone (PTH) have been associated with increased risks of hypertension, left ventricular hypertrophy, congestive heart failure, and cardiovascular mortality. Impaired arterial function is a potential mechanism for these associations. We tested whether serum PTH concentration is associated with measures of arterial function. DESIGN: Cross-sectional study. PARTICIPANTS: 6,545 persons without clinical cardiovascular disease participating in the community-based Multi-Ethnic Study of Atherosclerosis. MEASUREMENTS: Brachial artery flow-mediated dilation as well as aortic pulse pressure and arterial pulse parameters derived from Windkessel modeling of the radial pressure waveform. RESULTS: Higher serum PTH concentration was associated with lower brachial artery flow-mediated dilation (mean difference -0.09% per 10 pg/mL PTH), higher aortic pulse pressure (0.53 mmHg per 10 pg/mL), and reduced Windkessel capacitive index C1 (large artery elasticity, -0.12 ml/mmHg X 10 per 10 pg/mL), adjusting for potential confounding variables (all p-values ≤ 0.001). These relationships were independent of serum calcium concentration, serum 25-hydroxyvitamin D concentration, and estimated glomerular filtration rate and were consistent across relevant participant subgroups. Associations of PTH with aortic pulse pressure and capacitive index C1 were attenuated after adjustment for blood pressure. Serum PTH concentration was not associated with the oscillatory index C2 (small artery elasticity). CONCLUSIONS: Higher serum PTH concentration was associated with impaired endothelial function, increased aortic pulse pressure, and decreased capacitive index C1 in a large, diverse, community-based population. These relationships may help explain previously observed associations of elevated PTH with cardiovascular disease. © 2013 Blackwell Publishing Ltd.
Clinical Endocrinology 02/2013; · 3.17 Impact Factor
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ABSTRACT: The purpose of this study was to examine the associations of cardiovascular disease (CVD) risk with cognitive decline and incidence of dementia and cognitive impairment but not dementia (CIND) and the role of education as a modifier of these effects.
One thousand one hundred sixteen Mexican American elderly were followed annually in the Sacramento Area Latino Study on Aging. Our sex-specific 10-year CVD risk score included baseline age, systolic blood pressure, total cholesterol, high-density lipoprotein, smoking, body mass index, and diabetes. From adjusted linear mixed models, errors on the Modified Mini-Mental State Exam (3MSE) were annually 0.41% lower for women at the 25th percentile of CVD risk, 0.11% higher at the 50th percentile, and 0.83% higher at the 75th percentile (P value of CVDrisk×time <0.01). In men, 3MSE errors were annually 1.76% lower at the 25th percentile of CVD risk, 0.96% lower at the 50th percentile, and 0.12% higher at the 75th percentile (P value of CVDrisk×time <0.01). From adjusted linear mixed models, the annual decrease in the Spanish and English Verbal Learning Test score was 0.09 points for women at the 25th percentile of CVD risk, 0.10 points at the 50th percentile, and 0.12 points at the 75th percentile (P value of CVDrisk×time=0.02). From adjusted Cox models in women, compared with having <6 years of education, having 12+ years of education was associated with a 76% lower hazard of dementia/CIND (95% CI, 0.08 to 0.71) at the 25th percentile of CVD risk and with a 45% lower hazard (95% CI, 0.28 to 1.07) at the 75th percentile (P value of CVDrisk×education=0.05).
CVD risk score may provide a useful tool for identifying individuals at risk for cognitive decline and dementia.
Journal of the American Heart Association. 01/2013; 2(2):e004978.
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ABSTRACT: OBJECTIVES: Creatinine, the current clinical standard to detect chronic kidney disease (CKD), is biased by muscle mass, age and race. The authors sought to determine whether cystatin C, an alternative marker of kidney function less biased by these factors, can identify elderly Mexican Americans with CKD who are at high risk for death and cardiovascular disease. DESIGN: Longitudinal, with mean follow-up of 6.8 years. SETTING: Sacramento Area Latino Study of Aging (SALSA). PARTICIPANTS: One thousand four hundred and thirty five Mexican Americans aged 60 to 101. MEASUREMENTS: Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2) ) was determined according to creatinine (eGFRcreat) and cystatin C (eGFRcys), and participants were classified into four mutually exclusive categories: CKD neither (eGFRcreat ≥60 mL/min per 1.73 m(2) ; eGFRcys ≥60 mL/min per 1.73 m(2) ), CKD creatinine only (eGFRcreat <60 mL/min per 1.73 m(2) ; eGFRcys ≥60 mL/min per 1.73 m(2) ), CKD cystatin only (eGFRcreat ≥60 mL/min per 1.73 m(2) ; eGFRcys <60), and CKD both (eGFRcreat <60 mL/min per 1.73 m(2) ; GFRcys <60 mL/min per 1.73 m(2) ). The associations between each CKD classification and all-cause death and cardiovascular (CV) death were studied using Cox regression. RESULTS: At baseline, mean age was 71 ± 7; 481 (34%) had diabetes mellitus, and 980 (68%) had hypertension. Persons with CKD both had higher risk for all-cause (HR = 2.30, 95% confidence interval (CI) = 1.78-2.98) and CV disease (CVD) (HR = 2.75, 95% CI = 1.96-3.86) death than CKD neither after full adjustment. Persons with CKD cystatin C only were also at greater risk of all-cause (HR = 1.91, 95% CI = 1.37-2.67) and CV (HR = 2.56, 95% CI = 1.64-3.99) death than CKD neither. In contrast, persons with CKD creatinine only were not at greater risk for CV death (HR = 1.39, 95% CI = 0.71-2.72) but were at higher risk for all-cause death (HR = 1.95, 95% CI = 1.27-2.98). CONCLUSION: Cystatin C may be a useful alternative to creatinine for detecting high risk of death and CVD in elderly Mexican Americans with CKD.
Journal of the American Geriatrics Society 12/2012; · 3.74 Impact Factor
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ABSTRACT: The association of hypertension and mortality is attenuated in elderly adults. Walking speed, as a measure of frailty, may identify which elderly adults are most at risk for the adverse effects of hypertension. We hypothesized that elevated blood pressure (BP) would be associated with a greater risk of mortality in faster-, but not slower-, walking older adults.
Participants included 2340 persons 65 years and older in the National Health and Nutrition Examination Survey, 1999-2000 and 2001-2002. Mortality data were linked to death certificates in the National Death Index. Walking speed was measured over a 20-ft (6 m) walk and classified as faster (≥ 0.8 m/s [n = 1307]), slower (n = 790), or incomplete (n = 243). Potential confounders included age, sex, race, survey year, lifestyle and physiologic variables, health conditions, and antihypertensive medication use.
Among the participants, there were 589 deaths through December 31, 2006. The association between BP and mortality varied by walking speed. Among faster walkers, those with elevated systolic BP (≥ 140 mm Hg) had a greater adjusted risk of mortality compared with those without (hazard ratio [HR], 1.35; 95% CI, 1.03-1.77). Among slower walkers, neither elevated systolic nor diastolic BP (≥ 90 mm Hg) was associated with mortality. In participants who did not complete the walk test, elevated BP was strongly and independently associated with a lower risk of death: HR, 0.38; 95% CI, 0.23-0.62 (systolic); and HR, 0.10; 95% CI, 0.01-0.81 (diastolic).
Walking speed could be a simple measure to identify elderly adults who are most at risk for adverse outcomes related to high BP.
Archives of internal medicine 07/2012; 172(15):1162-8. · 11.46 Impact Factor
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ABSTRACT: BACKGROUND: Whether elevations in levels of urinary biomarkers of tubular injury (urine neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule 1 [KIM-1]) are associated with future risk of kidney disease has not been investigated. STUDY DESIGN: 1:1 nested case-control study. SETTING & PARTICIPANTS: 686 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). PREDICTOR: NGAL and KIM-1 were measured at baseline, expressed as log-transformed continuous variables, and categorized into deciles. OUTCOMES: Kidney function was estimated by cystatin C level using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Incident CKD stage 3 was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and an eGFR decrease >1 mL/min/1.73 m(2) per year, and rapid kidney function decrease was defined as decrease ≥3 mL/min/1.73 m(2) per year. MEASUREMENTS: Cases were defined as persons with eGFR >60 mL/min/1.73 m(2) who subsequently developed incident CKD stage 3 and/or had rapid kidney function decrease by the MESA year-5 visit. Controls were matched for age, sex, race, diabetes, and baseline eGFR. We adjusted for age, hypertension, and presence of albuminuria (albumin-creatinine ratio ≥30 mg/g). RESULTS: Of 343 cases, 145 had incident CKD stage 3, 141 had rapid kidney function decrease, and 57 had both. Mean eGFR for controls was 81 ± 10 mL/min/1.73 m(2) at baseline and 80 ± 10 mL/min/1.73 m(2) at follow-up compared with 82 ± 13 and 58 ± 10 mL/min/1.73 m(2) for cases. Each doubling of KIM-1 level (in picograms per milliliter) was associated with an OR of 1.15 (95% CI, 1.02-1.29) for incident CKD stage 3 and/or rapid kidney function decrease. Compared with the lowest 90%, the highest decile of KIM-1 level was associated with an OR of 2.02 (95% CI, 1.15-3.56) for the outcome; these associations were independent of albuminuria. NGAL levels (in nanograms per milliliter) were not associated with incident CKD stage 3 and/or rapid kidney function decrease (OR, 1.04; 95% CI, 0.99-1.10). Results were similar when KIM-1 and NGAL levels were standardized for urine creatinine. LIMITATIONS: The case-control design limits the ability to account for persons who died or were not available for follow-up. CONCLUSIONS: Urinary KIM-1 level is associated with future risk of kidney disease independent of albuminuria. Urinary biomarkers of tubular injury are a promising tool for identifying persons at risk of CKD.
American Journal of Kidney Diseases 06/2012; · 5.43 Impact Factor
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Shani Shastri,
Ronit Katz,
Dena E Rifkin,
Linda F Fried,
Michelle C Odden, Carmen A Peralta,
Michel Chonchol,
David Siscovick,
Michael G Shlipak,
Anne B Newman,
Mark J Sarnak
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ABSTRACT: To examine the association between kidney function and all-cause mortality in octogenarians.
Retrospective analysis of prospectively collected data.
Community.
Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.
Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.
Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (≥ 75 mL/min per 1.73 m(2) ) and lowest (≤ 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ).
Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .
Journal of the American Geriatrics Society 06/2012; 60(7):1201-7. · 3.74 Impact Factor
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ABSTRACT: Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated.
This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000-2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m(2) at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers.
Median decline was -0.8 (interquartile range, -3.1, -0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%-32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment.
Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations.
Clinical Journal of the American Society of Nephrology 05/2012; 7(7):1137-44. · 5.23 Impact Factor
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ABSTRACT: The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remain unclear, especially in a population-based setting.
Prospective observational study.
4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C-based estimate of glomerular filtration rate (eGFR(cys)) >60 mL/min/1.73 m(2) and at least one follow-up measurement of kidney function. All participants were free of cardiovascular disease at entry.
We evaluated the associations of C-reactive protein (CRP), interleukin 6 (IL-6), fibrinogen, factor VIII, and d-dimer levels with kidney function decrease.
Kidney function decrease was assessed primarily by repeated measurements of eGFR(cys) over 5 years. Rapid decrease in kidney function was defined as eGFR decrease >3 mL/min/1.73 m(2) per year. Incident low eGFR was defined as the onset of eGFR(cys) <60 mL/min/1.73 m(2) at any follow-up examination and eGFR(cys) decrease ≥1 mL/min/1.73 m(2) per year.
Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFR(cys) was 96 mL/min/1.73 m(2) and 7% had albuminuria. Median follow-up was 4.77 years. Higher factor VIII levels (per 1 standard deviation [SD] of biomarker) had the strongest association with kidney function decrease (β = -0.25; 95% CI, -0.38 to -0.12; P < 0.001), followed by IL-6 (β = -0.16; 95% CI, -0.29 to -0.03; P = 0.01), CRP (β = -0.09; 95% CI, -0.22 to 0.03; P = 0.1), and fibrinogen levels (β = -0.09; 95% CI, -0.22 to 0.04; P = 0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07-1.23), factor VIII (OR, 1.11; 95% CI, 1.03-1.18), and CRP (OR, 1.09; 95% CI, 1.02-1.16) at baseline was associated significantly with rapid kidney function decrease. Only IL-6 level was associated significantly with incident low eGFR (OR, 1.09; 95% CI, 1.00-1.19).
Observational study design and absence of measured GFR.
Inflammation and coagulation biomarkers are associated with decreasing kidney function in ambulatory adults without established cardiovascular disease or chronic kidney disease.
American Journal of Kidney Diseases 05/2012; 60(2):225-32. · 5.43 Impact Factor
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Ani Manichaikul,
Walter Palmas,
Carlos J Rodriguez, Carmen A Peralta,
Jasmin Divers,
Xiuqing Guo,
Wei-Min Chen,
Quenna Wong,
Kayleen Williams,
Kathleen F Kerr,
Kent D Taylor,
Michael Y Tsai,
Mark O Goodarzi,
Michèle M Sale,
Ana V Diez-Roux,
Stephen S Rich,
Jerome I Rotter,
Josyf C Mychaleckyj
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ABSTRACT: Using ~60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By projection of principal components (PCs) of ancestry to samples from the HapMap phase III and the Human Genome Diversity Panel (HGDP), we show the first two PCs quantify the Caucasian, African, and Native American origins, while the third and fourth PCs bring out an axis that aligns with known South-to-North geographic location of HGDP Native American samples and further separates MESA Mexican versus Central/South American samples along the same axis. Using k-means clustering computed from the first four PCs, we define four subgroups of the MESA Hispanic cohort that show close agreement with self-identification, labeling the clusters as primarily Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. To demonstrate our recommendations for genetic analysis in the MESA Hispanic cohort, we present pooled and stratified association analysis of triglycerides for selected SNPs in the LPL and TRIB1 gene regions, previously reported in GWAS of triglycerides in Caucasians but as yet unconfirmed in Hispanic populations. We report statistically significant evidence for genetic association in both genes, and we further demonstrate the importance of considering population substructure and genetic heterogeneity in genetic association studies performed in the United States Hispanic population.
PLoS Genetics 04/2012; 8(4):e1002640. · 8.69 Impact Factor
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ABSTRACT: Insulin resistance is a risk factor for cardiovascular and noncardiovascular diseases. Impaired kidney function is linked with insulin resistance and may affect relationships of insulin resistance with health outcomes.
We performed a cohort study of 3,138 Cardiovascular Health Study participants (age ≥ 65 years) without diabetes. Insulin sensitivity index (ISI) was calculated from fasting and 2-h postload insulin and glucose concentrations. Associations of ISI and fasting insulin concentration with all-cause mortality were tested using Cox proportional hazards models, adjusting for demographic variables, prevalent cardiovascular disease, lifestyle variables, waist circumference, and LDL cholesterol. Subsequent models were additionally adjusted for or stratified by glomerular filtration rate estimated using serum cystatin C (eGFR).
A total of 1,810 participants died during the 14.7-year median follow-up. Compared with the highest quartile of ISI, the lowest quartile (most insulin resistant) was associated with 21% (95% CI 6-41) and 11% (-3 to 29) higher risks of death without and with adjustment for eGFR, respectively. Compared with the lowest quartile of fasting insulin concentration, the highest quartile was associated with 22% (4-43) and 4% (-12 to 22) higher risks of death without and with adjustment for eGFR, respectively. Similar attenuation by eGFR was observed when blood pressure, triglycerides, HDL cholesterol, and C-reactive protein were included in models.
Insulin resistance measured as ISI or fasting insulin concentration is associated with increased risk of death among older adults, adjusting for conventional confounding characteristics. Impaired kidney function may mediate or confound this relationship.
Diabetes care 03/2012; 35(6):1355-60. · 8.09 Impact Factor
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ABSTRACT: In some older adults, higher blood pressure (BP) is associated with a lower risk of mortality. We hypothesized that higher BP would be associated with greater mortality in high-functioning elders and lower mortality in elders with lower functional status.
Participants were 1,562 Latino adults aged 60-101 years in the Sacramento Area Latino Study on Aging. Functional status was measured by self-reported walking speed, and BP was measured by automatic sphygmomanometer. Death information was determined from vital statistics records.
There were 442 deaths from 1998 to 2010; 53% were cardiovascular. Mean BP levels (mmHg) varied across fast, medium, and slow walkers: 136, 139, and 140 mmHg (systolic), p = .02 and 75, 76, and 77 mmHg (diastolic), p = .08, respectively. The relationship between systolic BP and mortality varied by self-reported walking speed: The adjusted hazard ratio for mortality in slow walkers was 0.96 per 10 mmHg higher systolic BP (95% confidence interval: 0.89, 1.02) and 1.29 (95% confidence interval: 1.08, 1.55) in fast walkers (p value for interaction <.001). We found a similar pattern for diastolic BP, although the interaction did not reach statistical significance; the adjusted hazard ratio per 10 mmHg higher diastolic BP was 0.89 (95% confidence interval: 0.78, 1.02) in slow walkers and 1.20 (95% confidence interval: 0.82, 1.76) in fast walkers (p value for interaction = .06).
In high-functioning older adults, elevated systolic BP is a risk factor for all-cause mortality. If confirmed in other studies, the assessment of functional status may help to identify persons who are most at-risk for adverse outcomes related to high BP.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 03/2012; 67(9):977-83. · 4.60 Impact Factor
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Joachim H Ix,
Ronit Katz,
Ian H de Boer,
Bryan R Kestenbaum, Carmen A Peralta,
Nancy S Jenny,
Matthew Budoff,
Matthew A Allison,
Michael H Criqui,
David Siscovick,
Michael G Shlipak
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ABSTRACT: Fetuin-A is a hepatic secretory protein that inhibits arterial calcification in vitro. The association of fetuin-A with coronary arterial calcification (CAC) in the general population is uncertain.
Among 2457 community-living individuals without cardiovascular disease (CVD), we measured serum fetuin-A concentrations by ELISA and evaluated the cross-sectional association of fetuin-A with CAC prevalence (any vs none) and severity; on follow-up 3.2 years (median) later, we evaluated the association of fetuin-A with CAC incidence and progression.
The mean age was 62 (SD 10) years, and the mean fetuin-A concentration was 0.48 (0.10) g/L. At baseline, 1200 individuals (49%) had CAC, and 272 individuals developed CAC during follow-up. At baseline, there was a threshold effect at the lowest fetuin-A quartile with CAC prevalence. In models adjusted for demographics, traditional cardiovascular disease (CVD) risk factors and kidney function, the lowest fetuin-A quartile had 7% (95% CI 1%-13%; P = 0.04) greater CAC prevalence compared with quartiles 2-4. Similar associations were observed with CAC severity at baseline, but the association was more linear. Each SD (0.10 g/L) lower fetuin-A was associated with a 12% (95% CI 3%-21%; P = 0.01) greater CAC severity in adjusted models. There was no significant association of fetuin-A with CAC incidence or progression.
Fetuin-A is inversely associated with CAC severity among community-living individuals without CVD. Whether fetuin-A concentrations are associated with incident CVD event in the general population requires future study.
Clinical Chemistry 02/2012; 58(5):887-95. · 7.91 Impact Factor
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ABSTRACT: Pentraxin-3 (PTX3) is an inflammatory marker thought to be more specific to vascular inflammation than C-reactive protein (CRP). Whether PTX3 is independently associated with adverse events among persons with stable coronary heart disease (CHD), independently of CRP, and whether kidney dysfunction influences these associations are not known.
We evaluated the associations of baseline PTX3 levels with all-cause mortality, cardiovascular (CV) events (myocardial infarction, stroke, or CHD death), and incident heart failure (HF) during 37 months among ambulatory persons with stable CHD participating in the Heart and Soul Study. Cox proportional hazards models were adjusted for age, sex, race, hypertension, diabetes, smoking, and CRP.
Among 986 persons with stable CHD, each 1 unit increase in log PTX3 at baseline was associated with an 80% increased risk of all-cause mortality (hazard ratio [HR] 1.8, 95% CI 1.5-2.1), a 50% increased risk of CV events (HR 1.5, 95% CI, 1.2-1.9), and an 80% greater risk of incident HF (HR 1.8, 95% CI, 1.3-2.5). Further adjustment for estimated glomerular filtration rate (eGFR) attenuated these associations to 1.6 (1.3-1.9) for mortality, 1.3 (1.0-1.6) for CV events and 1.5 (1.1-2.1) for incident HF. Stratification by eGFR >60 mL/min per 1.73m(2) or <60 mL/min per 1.73m(2) did not affect these associations (P interaction > .3 for all outcomes).
Among persons with stable CHD, higher PTX3 concentrations were associated with increased risk for all-cause mortality, CV events, and incident HF independently of systemic inflammation. Adjustment for eGFR modestly attenuated these associations, suggesting that future studies of PTX3 should adjust for kidney function.
American heart journal 02/2012; 163(2):274-9. · 4.65 Impact Factor
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ABSTRACT: Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known.
We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16,129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP ≥ 150 or DBP ≥ 90 mm Hg).
The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP ≥ 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP ≥ 150 mm Hg or DBP ≥ 90 mm Hg), mostly due to isolated systolic hypertension (54%).
In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD.
Archives of internal medicine 01/2012; 172(1):41-7. · 11.46 Impact Factor
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ABSTRACT: Higher serum phosphorus concentrations are associated with cardiovascular disease events and mortality. Low socioeconomic status is linked with higher serum phosphorus concentration, but the reasons are unclear. Poor individuals disproportionately consume inexpensive processed foods commonly enriched with phosphorus-based food preservatives. Accordingly, we hypothesized that excess intake of these foods accounts for a relationship between lower socioeconomic status and higher serum phosphorus concentration.
Cross-sectional analysis.
We examined a random cohort of 2,664 participants with available phosphorus measurements in the Multi-Ethnic Study of Atherosclerosis, a community-based sample of individuals free of clinically apparent cardiovascular disease from across the United States. PREDICTOR VARIABLES: Socioeconomic status, the intake of foods commonly enriched with phosphorus-based food additives (processed meats, sodas), and frequency of fast-food consumption.
Fasting morning serum phosphorus concentrations.
In unadjusted analyses, lower income and lower educational achievement categories were associated with modestly higher serum phosphorus concentration (by 0.02 to 0.10 mg/dL, P < .05 for all). These associations were attenuated in models adjusted for demographic and clinical factors, almost entirely due to adjustment for female gender. In multivariable-adjusted analyses, there were no statistically significant associations of processed meat intake or frequency of fast-food consumption with serum phosphorus. In contrast, each serving per day higher soda intake was associated with 0.02 mg/dL lower serum phosphorus concentration (95% confidence interval, -0.04, -0.01).
Greater intake of foods commonly enriched with phosphorus additives was not associated with higher serum phosphorus concentration in a community-living sample with largely preserved kidney function. These results suggest that excess intake of processed and fast foods may not impact fasting serum phosphorus concentrations among individuals without kidney disease.
Journal of Renal Nutrition 01/2012; 22(5):480-9. · 1.57 Impact Factor
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Carmen A Peralta,
David R Jacobs,
Ronit Katz,
Joachim H Ix,
Magdalena Madero,
Daniel A Duprez,
Mark J Sarnak,
Michael H Criqui,
Holly J Kramer,
Walter Palmas,
David Herrington,
Michael G Shlipak
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ABSTRACT: The association of subclinical vascular disease and early declines in kidney function has not been well studied.
Prospective cohort study.
Multi-Ethnic Study of Atherosclerosis (MESA) participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) with follow-up of 5 years.
Pulse pressure, small (SAE) and large arterial elasticity (LAE), and flow-mediated dilation.
Kidney function decline.
SAE and LAE were measured by pulse contour analysis of the radial artery. Kidney function was assessed by eGFR based on serum creatinine (eGFR(SCr)) and cystatin C (eGFR(SCysC)).
For 4,853 adults, higher pulse pressure and lower SAE and LAE had independent and linear associations with faster rates of kidney function decline. Compared with persons with pulse pressure of 40-50 mm Hg, eGFR(SCysC) declines were 0.29 (P = 0.006), 0.56 (P < 0.001), and 0.91 (P < 0.001) mL/min/1.73 m(2)/y faster in persons with pulse pressure of 50-60, 60-70, and >70 mm Hg, respectively. Compared with the highest quartile of SAE (most elastic), eGFR(SCysC) declines were 0.26 (P = 0.009), 0.35 (P = 0.001), and 0.70 (P < 0.001) mL/min/1.73 m(2)/y faster for the second, third, and fourth quartiles, respectively. For LAE, compared with the highest quartile, eGFR(SCysC) declines were 0.28 (P = 0.004), 0.58 (P < 0.001), and 0.83 (P < 0.001) mL/min/1.73 m(2)/y faster for each decreasing quartile of LAE. Findings were similar for eGFR(SCr). In contrast, for 2,997 adults with flow-mediated dilation and kidney function measures, flow-mediated dilation was not associated significantly with kidney function decline. For every 1-standard deviation greater flow-mediated dilation, eGFR(SCysC) and eGFR(SCr) changed by 0.05 (P = 0.3) and 0.06 mL/min/1.73 m(2)/y (P = 0.04), respectively.
We had no direct measure of GFR, in common with nearly all large population-based studies.
Higher pulse pressure and lower arterial elasticity, but not flow-mediated dilation, were associated linearly and independently with faster kidney function decline in persons with eGFR ≥60 mL/min/1.73 m(2). Future studies should investigate whether treatments to decrease the stiffness of large and small arteries may slow the rate of kidney function loss.
American Journal of Kidney Diseases 01/2012; 59(1):41-9. · 5.43 Impact Factor
