Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.

IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Urinary bisphenol A and obesity in U.S. children.

Childhood obesity, a major public health problem, can lead to cardiovascular disease in adulthood. Studies have implicated exposure to bisphenol A (BPA), a commonly used chemical, in the development of obesity in adults. However, literature is limited on this association in children. We examined the association between urinary BPA and obesity in children aged 6-18 years from the National Health and Nutrition Examination Survey (2003-2008). The primary exposure was urinary BPA and the outcome was obesity, defined as the ≥ 95th percentile of body mass index specific for age and sex. We found a positive association between increasing levels of urinary BPA and obesity, independent of age, sex, race/ethnicity, education, physical activity, serum cotinine, and urinary creatinine. Compared with children in the lowest quartile of BPA (<1.5 ng/mL), children in the highest quartile (>5.4 ng/mL) had a multivariable odds ratio for obesity of 2.55 (95% confidence interval (CI): 1.65, 3.95) (Ptrend < 0.01). The observed positive association was predominantly present in boys (odds ratio = 3.80, 95% CI: 2.25, 6.43) (Ptrend < 0.001) and in non-Hispanic whites (odds ratio = 5.87, 95% CI: 2.15, 16.05) (Ptrend < 0.01). In a representative sample of children, urinary BPA was associated with obesity, predominantly in non-Hispanic white boys, independent of major risk factors.

Positive association between perfluoroalkyl chemicals and hyperuricemia in children.

Hyperuricemia in children is associated with increased risk of high blood pressure, metabolic syndrome, and future cardiovascular disease. Serum perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) levels have been shown to be positively associated with hyperuricemia in adults, but the association in children remains unexplored. We therefore examined the association between serum PFOA and PFOS levels and hyperuricemia in a representative sample of US children. A cross-sectional study was performed on 1,772 participants ≤18 years of age from the National Health and Nutrition Examination Survey 1999-2000 and 2003-2008. The main outcome of interest was hyperuricemia, defined as serum uric acid levels ≥6 mg/dL. We found that serum levels of PFOA and PFOS were positively associated with hyperuricemia, independent of age, sex, race/ethnicity, body mass index, annual household income, physical activity, serum total cholesterol, and serum cotinine levels. Compared with subjects in quartile 1 (referent), subjects in quartile 4 had multivariable-adjusted odds ratios for hyperuricemia of 1.62 (95% confidence interval: 1.10, 2.37) for PFOA and 1.65 (95% confidence interval: 1.10, 2.49) for PFOS. Our findings indicate that serum perfluoroalkyl chemical levels are significantly associated with hyperuricemia in children even at the lower "background" exposure levels of the US general population.

Serum cystatin C and prediabetes in non-obese US adults.

Diabetes mellitus is the leading cause of end stage renal disease. Cystatin C, a marker of early renal impairment has been shown to be associated with diabetes. However, it is not clear if cystatin C is associated with prediabetes, an early stage in the hyperglycemic continuum where prevention efforts have been shown to be effective in delaying or preventing the onset of diabetes. We examined 2,033 participants from the National Health and Nutrition Examination Survey 1999-2002, aged ≥ 20 years (female 47.2 %) who were free of diabetes mellitus, chronic kidney disease and with body mass index <30 kg/m(2). Prediabetes (n = 541) was defined as a 2-h glucose concentration of 140-199 mg/dL, or a fasting glucose concentration of 110-125 mg/dL, or an A1C value of 5.7-6.4 %. Cystatin C levels were categorized into gender-specific quartiles for analysis. Elevated levels of serum cystatin C were associated with prediabetes after adjusting for potential confounders including serum total cholesterol, systolic blood pressure, body mass index and C-reactive protein. Compared to those with cystatin C in the lowest quartile, the multivariable odds ratio (95 % confidence interval) of prediabetes among those in the highest quartile was 2.08 (1.09-3.97), p for trend = 0.02. Although, this association was stronger among women and non-Hispanic whites, there was no significant interaction by sex (p = 0.1) or by race-ethnicity (p = 0.6). Our findings suggest that elevated levels of serum cystatin C are associated with prediabetes in a nationally representative sample of non-obese US adults.

Cardio-metabolic risk factors and prehypertension in persons without diabetes, hypertension, and cardiovascular disease.

BACKGROUND: Prehypertension has been shown to be an early risk factor of cardiovascular disease (CVD). We investigated the prevalence and pattern of cardiometabolic risk factors in prehypertension in three ethnic Asian populations in Singapore. METHODS: We examined data from Chinese (n=1177), Malay (n=774), and Indian (n=985) adults aged 40-80 years who participated in three independent population based studies conducted from 2004-2011 in Singapore who were free of diabetes, hypertension and previous CVD. Prehypertension was defined as systolic blood pressure (BP) 120-139 mm Hg or diastolic BP 80-89 mm Hg. Random blood glucose, glycated haemoglobin (HbA1c), body mass index (BMI), triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were examined as indicators of adverse cardiometabolic profile. The association between metabolic variables and prehypertension was examined using logistic regression models adjusting for potential confounders. RESULTS: The prevalence of prehypertension was 59.8% (Chinese), 68.9% (Malays) and 57.7% Indians. Higher levels of blood glucose, HbA1c and BMI were significantly associated with prehypertension in all three ethnic groups, odds ratio (95% confidence interval) of prehypertension in Chinese, Malays and Indians were: 1.42 (1.10, 1.83), 1.53 (1.05, 2.24), 1.49 (1.13, 1.98) for high-glucose; 3.50 (1.01, 12.18), 3.72 (1.29, 10.75), 2.79 (1.31, 5.94) for high-HbA1c; 1.86 (1.34, 2.56), 2.96 (2.10, 4.18), 1.68 (1.28, 2.20) for high-BMI. In addition, higher levels of LDL cholesterol in Chinese and higher levels of triglycerides were significantly associated with prehypertension. These associations persisted when metabolic variables were analysed as continuous variables. CONCLUSIONS: Higher levels of blood glucose, HbA1c and BMI were associated with prehypertension in all three ethnic groups in Singapore. Screening for prehypertension and lifestyle modifications could potentially reduce the burden of CVD in otherwise healthy Asian adults living in Singapore.

Combined effect of lung function level and decline increases morbidity and mortality risks.

Lung function level and decline are each predictive of morbidity and mortality. Evaluation of the combined effect of these measurements may help further identify high-risk groups. Using Copenhagen City Heart Study longitudinal spirometry data (n = 10,457), 16-21 year risks of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease mortality, and all-cause mortality were estimated from combined effects of level and decline in forced expiratory volume in one second (FEV(1)). Risks were evaluated using Cox proportional hazards models for individuals grouped by combinations of baseline predicted FEV(1) and quartiles of slope. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using stratified analysis by gender, smoking status, and baseline age (≤45 and >45). For COPD morbidity, quartiles of increasing FEV(1) decline increased HRs (95 % CI) for individuals with FEV(1) at or above the lower limit of normal (LLN) but below 100 % predicted, reaching 5.11 (2.58-10.13) for males, 11.63 (4.75-28.46) for females, and 3.09 (0.88-10.86) for never smokers in the quartile of steepest decline. Significant increasing trends were also observed for mortality and in individuals with a baseline age ≤45. Groups with 'normal' lung function (FEV(1) at or above the LLN) but excessive declines (fourth quartile of FEV(1) slope) had significantly increased mortality risks, including never smokers and individuals with a baseline age ≤45.

Serum vitamin D level and prehypertension among subjects free of hypertension.

BACKGROUND: Low serum vitamin D levels are associated with high blood pressure (BP). Prehypertension is a preclinical stage where primary prevention efforts have been recommended for delaying or preventing the onset of hypertension. However, the majority of studies examining the association between vitamin D and BP have not accounted for kidney function or systemic inflammation. METHODS: Participants of the 3rd National Health and Nutrition Examination Survey > 20 years of age and free of hypertension (n = 9,215, 53.5% women) and clinical cardiovascular disease were examined. Serum vitamin D levels were analyzed as quartiles. Prehypertension (n = 3,712) was defined as systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg. RESULTS: Lower serum vitamin D levels were found to be associated with prehypertension independent of potential confounders including body mass index (BMI), serum cholesterol, C-reactive protein and estimated glomerular filtration rate. Compared to the highest quartile of serum vitamin D (referent), the odds ratio (95% confidence interval) of prehypertension associated with the lowest quartile was 1.48 (1.16-1.90; p trend < 0.0001). This association persisted in subgroup analyses by gender, race-ethnicity and BMI. CONCLUSION: Lower serum vitamin D levels are associated with prehypertension in a representative sample of US adults.

Income is a stronger predictor of mortality than education in a national sample of US adults.

Low socioeconomic status (SES) is associated with mortality in several populations. SES measures, such as education and income, may operate through different pathways. However, the independent effect of each measure mutually adjusting for the effect of other SES measures is not clear. The association between poverty-income ratio (PIR) and education and all-cause mortality among 15,646 adults, aged >20 years, who participated in the Third National Health and Nutrition Examination Survey in the USA, was examined. The lower PIR quartiles and less than high school education were positively associated with all-cause mortality in initial models adjusting for the demographic, lifestyle and clinical risk factors. After additional adjustment for education, the lower PIR quartiles were still significantly associated with all-cause mortality. The multivariable odds ratio (OR) [95% confidence interval (CI)] of all-cause mortality comparing the lowest to the highest quartile of PIR was 2.11 (1.52-2.95, p trend < or = 0.0001). In contrast, after additional adjustment for income, education was no longer associated with all-cause mortality [multivariable OR (95% CI) of all-cause mortality comparing less than high school to more than high school education was 1.05 (0.85-1.31, p trend=0.57)]. The results suggest that income may be a stronger predictor of mortality than education, and narrowing the income differentials may reduce the health disparities.

Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.

CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

The relationship between gamma-glutamyl transferase levels and chronic kidney disease among Appalachian adults.

BACKGROUND: Serum gamma-glutamyl transferase (GGT), a marker of oxidative stress has been associated with diabetes and hypertension, which are risk factors for chronic kidney disease (CKD). However, it is unclear whether serum GGT is independently associated with CKD. METHODS: We analyzed data from a population-based study of Appalachian adults residing in six communities in Ohio and West Virginia, who were aged > or = 18 years (n = 55,187, 52% women). Serum GGT was examined as gender-specific quintiles (quintiles 1-5 in women: 0-11 U/L, 12-14 U/L, 15-19 U/L, 20-29 U/L and > 29 U/L; quintiles 1-5 in men: 0-17 U/L, 18-23 U/L, 24-30 U/L, 31-45 U/L, and > 45 U/L). The main outcome of interest was CKD (n = 4482), defined as an estimated glomerular filtration rate of < 60 mL/ min/1.73 m2 from serum creatinine. RESULTS: Higher serum GGT levels were not found to be associated with CKD after adjusting for age, education, smoking, alcohol intake, body mass index (BMI), diabetes, hypertension and total cholesterol. In women, compared to quintile 1 of GGT, the odds ratio (OR) (95% confidence interval [CI]) of CKD associated with quintile 5 was 0.93 (0.82-1.06); p-trend = 0.3102. Similarly, in men, compared to quintile 1 of GGT, the odds ratio (OR) (95% confidence interval [CI]) of CKD associated with quintile 5 was 0.94 (0.80-1.10); p-trend = 0.4372. Subgroup analyses that examined the relation between GGT and CKD by alcohol intake and BMI categories also showed a consistent null association. CONCLUSION: In a community-based sample of Appalachian adults, higher serum GGT was not found to be independently associated with CKD.

Perfluoroalkyl chemicals and chronic kidney disease in US adults.

Chronic kidney disease (CKD) is a major public health problem. Identifying novel risk factors for CKD, including widely prevalent environmental exposures, is therefore important. Perfluoroalkyl chemicals (PFCs), including perfluorooctanoic acid and perfluorooctane sulfonate, are manmade chemicals that have been detected in the blood of more than 98% of the US population. Results from experimental animal studies have suggested that an association between PFCs and CKD is plausible. However, in humans, the relation between serum PFCs and CKD has not been examined. The authors examined the relation of serum PFCs and CKD in 4,587 adult participants (51.1% women) from the combined 1999-2000 and 2003-2008 cycles of the National Health and Nutritional Examination Survey for whom PFC measurements were available. The main outcome was CKD, defined as a glomerular filtration rate of less than 60 mL/minute/1.73 m(2). The authors found that serum levels of PFCs, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with CKD. This association was independent of confounders such as age, sex, race/ethnicity, body mass index, diabetes, hypertension, and serum cholesterol level. Compared with subjects in quartile 1 (referent), the multivariable odds ratio for CKD among subjects in quartile 4 was 1.73 (95% confidence interval: 1.04, 2.88; P for trend = 0.015) for perfluorooctanoic acid and 1.82 (95% confidence interval: 1.01, 3.27; P for trend = 0.019) for perfluorooctane sulfonate. The present results suggest that elevated PFC levels are associated with CKD.

Association of osteoarthritis with serum levels of the environmental contaminants perfluorooctanoate and perfluorooctane sulfonate in a large Appalachian population.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the pathogenesis of osteoarthritis (OA). However, the link between these compounds and OA remains unknown. In this study, the authors investigated the association of OA with PFOA and PFOS in a population of 49,432 adults from 6 PFOA-contaminated water districts in the mid-Ohio Valley (2005-2006). Participants completed a comprehensive health survey; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history, including physician diagnosis of osteoarthritis, was assessed via self-report. Analyses included adjustment for demographic and lifestyle characteristics, body mass index, and other potential confounders. Reported OA showed a significant positive association with PFOA serum levels (for highest quartile of PFOA vs. lowest, adjusted odds ratio = 1.3, 95% confidence interval: 1.2, 1.5; P-trend = 0.00001) and a significant inverse association with PFOS (for highest quartile vs. lowest, adjusted odds ratio = 0.8, 95% confidence interval: 0.7, 0.9; P-trend = 0.00005). The relation between PFOA and OA was significantly stronger in younger and nonobese adults. Although the cross-sectional nature of this large, population-based study limits causal inference, the observed strong, divergent associations of reported OA with PFOA and PFOS may have important public health and etiologic implications and warrant further investigation.

Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study.

In animal models, inflammatory processes have been shown to have an important role in the development of kidney disease. In humans, however, the independent relation between markers of inflammation and the risk of chronic kidney disease (CKD) is not known. To clarify this, we examined the relationship of several inflammatory biomarker levels (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, white blood cell count, and interleukin-6) with the risk of developing CKD in a population-based cohort of up to 4926 patients with 15 years of follow-up. In cross-sectional analyses, we found that all these inflammation markers were positively associated with the outcome of interest, prevalent CKD. However, in longitudinal analyses examining the risk of developing incident CKD among those who were CKD-free at baseline, only tumor necrosis factor-α receptor 2, white blood cell count, and interleukin-6 levels (hazard ratios comparing highest with the lowest tertile of 2.10, 1.90, and 1.45, respectively), and not C-reactive protein (hazard ratio 1.09), were positively associated with incident CKD. Thus, elevations of most markers of inflammation predict the risk of developing CKD. Each marker should be independently verified.

Retinal microvascular changes and the risk of developing obesity: population-based cohort study.

BACKGROUND: Recent studies have hypothesized that endothelial and microvascular dysfunction may play a role in the development of obesity. Previous studies have shown that retinal microvascular changes are associated with diabetes, hypertension, and cardiovascular disease. In contrast, few prospective studies have examined the association between retinal microvascular changes and the risk of developing obesity. METHODS: We examined n = 2089 nonobese subjects from a population-based cohort in Beaver Dam, Wisconsin (aged 44-85 years, 49% women). Retinal arteriolar and venular diameters were measured from baseline retinal photographs. The main outcome-of-interest was 15-year incidence of obesity. RESULTS: Retinal venular widening was positively associated with incident obesity over a 15-year follow-up period. This association was independent of age, gender, smoking, alcohol intake, education, physical activity, body mass index, serum cholesterol, and C-reactive protein levels. Compared with subjects with retinal venular diameter in the lowest tertile (referent), the multivariable relative risk (95% confidence interval) of obesity among subjects in the highest tertile was 1.68 (1.24-2.28); p-trend = 0.0005. In contrast, narrow retinal arterioles were not associated with obesity. CONCLUSIONS: In a population-based cohort, we found that wider retinal venules are positively associated with risk of developing obesity, suggesting a role for microvascular dysfunction in its etiology.

Bidirectional association of retinal vessel diameters and estimated GFR decline: the Beaver Dam CKD Study.

BACKGROUND: Recent cross-sectional studies have reported an association between retinal vessel caliber and chronic kidney disease (CKD), but the direction of the association between these 2 processes is not clear. In a prospective study with multiple measurements of retinal vessel diameters and serum creatinine, we examined whether baseline retinal vessel diameter is associated with future risk of decreased kidney function, or vice versa. STUDY DESIGN: Population-based cohort study. SETTING & PARTICIPANTS: 3,199 Wisconsin adults aged 43-84 years who were followed up prospectively for 15 years. PREDICTOR: Baseline retinal arteriolar and venular diameters for analysis 1 and baseline estimated glomerular filtration rate (eGFR) categories for analysis 2. OUTCOMES & MEASUREMENTS: For analysis 1, incident CKD, defined as eGFR <60 mL/min/1.73 m(2) accompanied by a 25% decrease in eGFR, during follow-up. For analysis 2, incident retinal arteriolar narrowing, defined as a central retinal arteriolar equivalent measurement <144.0 µm, and incident retinal venular dilation, defined as a central retinal venular equivalent measurement >243.8 µm. RESULTS: Baseline retinal arteriolar and venular diameters were not associated with 15-year risk of incident CKD. After adjustment for age, sex, diabetes, hypertension, and other confounders, the multivariable HR of incident CKD comparing the narrowest with the widest quartile was 1.15 (95% CI, 0.74-1.80) for retinal arteriolar diameter and 1.05 (95% CI, 0.67-1.67) for retinal venular diameter. Similarly, there was no significant association between eGFR and 15-year risk of incident retinal arteriolar narrowing or retinal venular widening. Compared with eGFR >90 mL/min/1.73 m(2) (referent), the multivariable HR for those with eGFR <45 mL/min/1.73 m(2) was 1.66 (95% CI, 0.93-2.96) for incident retinal arteriolar narrowing and 0.60 (95% CI, 0.17-1.85) for retinal venular widening. LIMITATIONS: Lack of data for albuminuria and loss to follow-up. CONCLUSIONS: Retinal vessel diameters and CKD may run together through shared mechanisms, but are not causally related.

Socioeconomic status, self-rated health, and mortality in a multiethnic sample of US adults.

OBJECTIVE: To examine the association between socioeconomic status (SES), self-rated health (SRH), and mortality separately by race-ethnicity in a nationally representative sample of US adults. METHODS: We analyzed data from 16 716 adult women and men who were followed up for mortality for up to 12 years as part of the third National Health and Nutrition Examination survey (NHANES III). Poverty-income ratio (PIR) and education were assessed as measures of SES. All-cause mortality (n = 2850) was recorded from the NHANES III linked mortality file. RESULTS: Lower PIR was associated with mortality after adjustment for lifestyle, clinical risk factors, and SRH in all racial-ethnic groups (P-trend <0.005). In contrast, after adjusting for lifestyle and clinical risk factors, lower education was not associated with all-cause mortality in non-Hispanic whites (P-trend = 0.16), whereas the association remained significant after adjustment for SRH and lifestyle and clinical risk factors in other race-ethnicities (P-trend = 0.005; P-interaction between education categories and race-ethnicity was 0.02). CONCLUSIONS: Our results suggest that lower PIR was associated with mortality in all racial-ethnic groups. In contrast, lower education was significantly associated with mortality only in racial-ethnic groups other than non-Hispanic whites. Our results indicate that, beyond lifestyle and clinical risk factors, adjusting for SRH resulted in only a modest change in the association of SES and mortality.

Association between plasma homocysteine and microalbuminuria in persons without hypertension, diabetes mellitus, and cardiovascular disease.

BACKGROUND: Microalbuminuria and plasma homocysteine levels are both considered to be markers of endothelial dysfunction and shown to be predictors of cardiovascular disease (CVD) in epidemiological studies. However, previous studies examining the association between plasma homocysteine and microalbuminuria have suggested that this association is explained by confounding factors such as preexisting CVD, diabetes, hypertension, and reduced kidney function. METHODS: We examined the association between plasma homocysteine and microalbuminuria in a representative sample of US men and women aged ≥ 20 years, who were free of diabetes mellitus, hypertension, and CVD and who participated in the Third National Health and Nutrition Examination Survey (n = 3,948). Microalbuminuria was defined as urinary albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS: Plasma homocysteine levels were positively associated with microalbuminuria in men but not in women (p-interaction <0.0001) after adjusting for age, race/ethnicity, smoking, drinking, body mass index, physical activity, glomerular filtration rate, blood pressure, high-density lipoprotein cholesterol, glycated hemoglobin, serum folate, serum vitamin B(12), and C-reactive protein. In men, the multivariable odds ratio (OR) [95% confidence interval (CI)] of microalbuminuria comparing the highest to the lowest quartile of homocysteine was 5.17 (2.00-13.36); (p-trend = 0.005). Further, men in the highest quartile of homocysteine and age ≥ 60 years had >12-fold odds of microalbuminuria compared with men in the lowest homocysteine quartile and age <60 years. In contrast, in women, the multivariable OR (95% CI) comparing the highest to the lowest quartile of homocysteine was 0.96 (0.86-1.07); (p-trend = 0.41). CONCLUSIONS: Among relatively healthy adults, plasma homocysteine levels are associated with microalbuminuria only in men.

Sleep duration and cardiovascular disease: results from the National Health Interview Survey.

BACKGROUND: Previous studies have shown that both short and long sleep durations are related to increased likelihood of diabetes and hypertension. However, the relation between sleep duration and cardiovascular disease (CVD) is not clear. We examined the hypothesis that compared with sleep duration of 7 hours, shorter and longer sleep durations are independently related to CVD. METHODS: We conducted a cross-sectional study of 30,397 National Health Interview Survey 2005 participants > or = 18 years of age (57.1% women). Sleep duration was categorized as < or = 5 hours, 6 hours, 7 hours, 8 hours, and > or = 9 hours. The main outcome of interest was the presence of any CVD (n = 2146), including myocardial infarction, angina, and stroke. RESULTS: We found both short and long sleep durations to be independently associated with CVD, independent of age, sex, race-ethnicity, smoking, alcohol intake, body mass index, physical activity, diabetes mellitus, hypertension, and depression. Compared with a sleep duration of 7 h (referent), the multivariate odds ratio (95% confidence interval) of CVD was 2.20 (1.78, 2.71), 1.33 (1.13, 1.57), 1.23 (1.06, 1.41), and 1.57 (1.31, 1.89) for sleep duration < or = 5 h, 6 h, 8 h, and > or = 9 h. This association persisted in subgroup analyses by gender, race-ethnicity, and body mass index categories. Also, similar associations were observed when we examined myocardial infarction and stroke separately. CONCLUSION: Compared with sleep duration of 7 h, there was a positive association between both shorter and longer sleep durations and CVD in a representative sample of US adults. These results suggest that sleep duration may be an important marker of CVD.

Higher serum uric acid associated with decreased Parkinson's disease prevalence in a large community-based survey.

A large community-based cross-sectional survey provided an opportunity to evaluate a previously reported association between Parkinson's disease (PD) and low serum uric acid (UA) levels in this population. The association between a self-reported PD diagnosis with treatment (n = 59) and serum UA level was examined using logistic and linear regression models, controlling for key covariates. In adjusted models, participants with UA levels at or above the median had a significantly lower odds of reporting PD with treatment compared with those with lower UA levels (OR 0.33, 95% CI 0.19-0.60, P = 0.0002). This association was observed for both men and women. The mean UA level among participants reporting PD with treatment was 0.78 mg/dl lower than the mean UA level among those not reporting PD (P

The relationship between serum uric acid and chronic kidney disease among Appalachian adults.

BACKGROUND: Higher serum uric acid (SUA) levels have been shown to be associated with cardiovascular disease. SUA levels are also associated with hypertension, a strong risk factor for chronic kidney disease (CKD). However, it is unclear whether SUA is independently associated with CKD. We examined the hypothesis that higher SUA levels are positively associated with CKD. METHODS: We analysed data from the C8 Health Study, a population-based study of Appalachian adults aged ≥18 years and free of cardiovascular disease (n = 49,295, 53% women). SUA was examined as gender-specific quartiles. The outcome of interest was CKD (n = 2,980), defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m(2) from serum creatinine. RESULTS: Overall, we observed a clear positive association between increasing quartiles of SUA and CKD, independent of confounders. Compared with the lowest quartile of SUA (referent), the multivariable odds ratios (95% confidence interval) for quartiles 2-4, respectively, of CKD were 1.53 (1.31, 1.78), 2.16 (1.86 2.50) and 4.67 (4.07, 5.36); P-trend < 0.0001. This observed positive association persisted in separate analysis among men (P-trend < 0.0001) and women (P-trend < 0.0001). CONCLUSIONS: In conclusion, higher SUA levels are positively associated with CKD, suggesting that at least part of the reported association between SUA and cardiovascular disease may be mediated by CKD.