Risk prediction of major complications in individuals with diabetes: the Atherosclerosis Risk in Communities Study.

AIMS: To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers. METHODS: We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics. RESULTS: Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [ß-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%). CONCLUSIONS: These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.

Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communities (ARIC) Study.

AIMS: To examine the associations of the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase(AST), and gamma-glutamyl transferase (GGT) with diabetes risk and to determine whether associations differ by race and/or gender. We hypothesized that all liver enzymes would be associated with diabetes risk and that associations would differ by race and gender. METHODS: Prospective cohort of 7495 white and 1842 black participants without diabetes in the Atherosclerosis Risk in Communities Study. Poisson and Cox models adjusted for demographic, socio-behavioural, and metabolic and health-related factors were used. RESULTS: During a median of 12 years of follow-up, 2182 incident cases of diabetes occurred. Higher liver enzyme levels were independently associated with diabetes risk: adjusted hazard ratios (95% confidence intervals) were 1.68 (1.49-1.89), 1.16 (1.02-1.31) and 1.95 (1.70-2.24) comparing the highest with the lowest quartiles of ALT, AST, and GGT, respectively. Gamma-Glutamyl transferase was most strongly related to diabetes risk, even at levels considered within the normal range (≤ 60 U/l) in clinical practice. Adjusted incidence rates by quartiles of liver enzymes were similar by gender but higher in black versus white participants. Nonetheless, relative associations of ALT, AST, and GGT with diabetes were similar by race (P for interactions > 0.05). CONCLUSIONS: Compared with ALT and AST, GGT was more strongly associated with diabetes risk. Our findings suggest that abnormalities in liver enzymes precede the diagnosis of diabetes by many years and that individuals with elevated liver enzymes, even within the normal range as defined in clinical practice, are at high risk for diabetes.

Early hospital readmission after kidney transplantation: patient and center-level associations.

Early hospital readmission (EHR) is associated with increased morbidity, costs and transition-of-care errors. We sought to quantify rates of and risk factors for EHR after kidney transplantation (KT). We studied 32 961 Medicare primary KT recipients (2000-2005) linked to Medicare claims through the United States Renal Data System. EHR was defined as at least one hospitalization within 30 days of initial discharge after KT. The association between EHR and recipient and transplant factors was explored using Poisson regression; hierarchical modeling was used to account for study center-level differences. The overall EHR rate was 31%, and 19 independent patient-level factors associated with EHR were identified: recipient factors included older age, African American race and various comorbidities; transplant factors included ECD, length of stay and lack of induction therapy. The unadjusted rate of EHR by center ranged from 18% to 47%, but conventional center-level factors (percent African American, percent age > 60, percent deceased donor and percent expanded criteria donor) were not associated with EHR. However, intermediate total volume and average length of stay were associated with increased EHR risk. Better identification of patients at risk for early hospital readmission following KT may guide discharge planning and early posttransplant outpatient monitoring.

Risk factors for lacune subtypes in the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Lacunar infarctions are mainly due to 2 microvascular pathologies: lipohyalinosis and microatheroma. Little is known about risk factor differences for these subtypes. We hypothesized that diabetes and glycated hemoglobin (HbA(1)c) would be related preferentially to the lipohyalinotic subtype. METHODS: We performed a cross-section analysis of the brain MRI data from 1,827 participants in the Atherosclerosis Risk in Communities study. We divided subcortical lesions ≤ 20 mm in diameter into those ≤ 7 mm (of probable lipohyalinotic etiology) and 8-20 mm (probably due to microatheroma) and used Poisson regression to investigate associations with the number of each type of lesion. Unlike previous studies, we also fitted a model involving lesions <3 mm. RESULTS: Age (prevalence ratio [PR] 1.11 per year; 95% confidence interval [CI] 1.08-1.14), black ethnicity (vs white, PR 1.66; 95% CI 1.27-2.16), hypertension (PR 2.12; 95% CI 1.61-2.79), diabetes (PR 1.42; 95% CI 1.08-1.87), and ever-smoking (PR 1.34; 95% CI 1.04-1.74) were significantly associated with lesions ≤ 7 mm. Findings were similar for lesions <3 mm. HbA(1)c, substituted for diabetes, was also associated with smaller lesions. Significantly associated with 8-20 mm lesions were age (PR 1.14; 95% CI 1.09-1.20), hypertension (PR 1.79; 95% CI 1.14-2.83), ever-smoking (PR 2.66; 95% CI 1.63-4.34), and low-density lipoprotein (LDL) cholesterol (PR 1.27 per SD; 95% CI 1.06-1.52). When we analyzed only participants with lesions, history of smoking (PR 1.99; 95% CI 1.23-3.20) and LDL (PR 1.33 per SD; 95% CI 1.08-1.65) were associated with lesions 8-20 mm. CONCLUSIONS: Smaller lacunes (even those <3 mm) were associated with diabetes and HbA(1)c, and larger lacunes associated with LDL cholesterol, differences which support long-held theories relating to their underlying pathology. The findings may contribute to broader understanding of cerebral microvascular disease.

Glycated haemoglobin and cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: This study aimed to examine the association between diabetes and hyperglycaemia-assessed by HbA(1c)-and change in cognitive function in persons with and without diabetes. METHODS: This was a prospective cohort study of 8,442 non-diabetic and 516 diabetic participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined the association of baseline categories of HbA(1c) with 6 year change in three measures of cognition: the digit symbol substitution test (DSST); the delayed word recall test (DWRT); and the word fluency test (WFT). Our primary outcomes were the quintiles with the greatest annual cognitive decline for each test. Logistic regression models were adjusted for demographic (age, sex, race, field centre, education, income), lifestyle (smoking, drinking) and metabolic (adiposity, blood pressure, cholesterol) factors. RESULTS: The mean age was 56 years. Women accounted for 56% of the study population and 21% of the study population were black. The mean HbA(1c) was 5.7% overall: 8.5% in persons with and 5.5% in persons without diabetes. In adjusted logistic regression models, diagnosed diabetes was associated with cognitive decline on the DSST (OR 1.42, 95% CI 1.14-1.75, p = 0.002), but HbA(1c) was not a significant independent predictor of cognitive decline when stratifying by diabetes diagnosis (diabetes, p trend = 0.320; no diabetes, p trend = 0.566). Trends were not significant for the DWRT or WFT in either the presence or the absence of diabetes. CONCLUSIONS/INTERPRETATION: Hyperglycaemia, as measured by HbA(1c), did not add predictive power beyond diabetes status for 6 year cognitive decline in this middle-aged population. Additional work is needed to identify the non-glycaemic factors by which diabetes may contribute to cognitive decline.

NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: To validate the reported association between rs10494366 in NOS1AP (the gene encoding nitric oxide synthase-1 adaptor protein) and the incidence of type 2 diabetes in calcium channel blocker (CCB) users and to identify additional NOS1AP variants associated with type 2 diabetes risk. METHODS: Data from 9 years of follow-up in 9,221 middle-aged white and 2,724 African-American adults free of diabetes at baseline from the Atherosclerosis Risk in Communities study were analysed. Nineteen NOS1AP variants were examined for associations with incident diabetes and fasting glucose levels stratified by baseline CCB use. RESULTS: Prevalence of CCB use at baseline was 2.7% (n = 247) in whites and 2.3% (n = 72) in African-Americans. Among white CCB users, the G allele of rs10494366 was associated with lower diabetes incidence (HR 0.57, 95% CI 0.35-0.92, p = 0.016). The association was marginally significant after adjusting for age, sex, obesity, smoking, alcohol use, physical activity, hypertension, heart rate and electrocardiographic QT interval (HR 0.63, 95% CI 0.38-1.04, p = 0.052). rs10494366 was associated with lower average fasting glucose during follow-up (p = 0.037). No other variants were associated with diabetes risk in CCB users after multiple-testing correction. No associations were observed between any NOS1AP variant and diabetes development in non-CCB users. NOS1AP variants were not associated with diabetes risk in either African-American CCB users or non-CCB users. CONCLUSIONS/INTERPRETATION: We have independently replicated the association between rs10494366 in NOS1AP and incident diabetes among white CCB users. Further exploration of NOS1AP variants and type 2 diabetes and functional studies of NOS1AP in type 2 diabetes pathology is warranted.

Retinal microvascular abnormalities and cognitive decline: the ARIC 14-year follow-up study.

BACKGROUND: Because retinal and cerebral arterioles share similar pathologic processes, retinal microvascular changes are expected to be markers of cerebral small vessel disease (SVD). To better understand the role of SVD in cognitive function, we investigated the relationship between retinal microvascular abnormalities and longitudinal changes in cognitive function in a community-based study. METHODS: A total of 803 participants underwent 4 cognitive assessments between 1990-1992 and 2004-2006, using the Word Fluency (WF) test, Digit Symbol Substitution (DSS), and Delayed Word Recall as well as retinal photography in 1993-1995. Covariate adjusted random effects linear models for repeated measures were used to determine the associations of cognitive change with specific retinal vascular abnormalities. RESULTS: Individuals with retinopathy showed declines in executive function and psychomotor speed, with 1) an average decline in WF of -1.64 words per decade (95% confidence interval [CI] -3.3, -0.02) compared to no decline in those without retinopathy +0.06 (95% CI -0.6, 0.8) and 2) a higher frequency of rapid decliners on the DSS test. CONCLUSION: Signs of retinal vascular changes, as markers of the cerebral microvasculature, are associated with declines in executive function and psychomotor speed, adding to the growing evidence for the role of microvascular disease in cognitive decline in the elderly.

Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Cardiovascular risk factors are associated with a higher risk of developing dementia. Studies in older populations, however, have often failed to show this relationship. We assessed the association between cardiovascular risk factors measured in midlife and risk of being hospitalised with dementia and determined whether this association was modified by age and ethnicity. METHODS: We studied 11 151 participants in the population-based Atherosclerosis Risk in Communities cohort, aged 46-70 (23% African-Americans) in 1990-2, when participants underwent a physical exam and cognitive testing. Hospitalisations with dementia were ascertained through December 2004. RESULTS: During follow-up, 203 cases of hospitalisation with dementia were identified. Smoking (hazard ratio (HR), 95% CI 1.7, 1.2 to 2.5), hypertension (HR, 95% CI 1.6, 1.2 to 2.2) and diabetes (HR, 95% CI 2.2, 1.6 to 3.0) were strongly associated with dementia, in Caucasians and African-Americans. These associations were stronger when risk factors were measured at a younger age than at an older age. In analyses including updated information on risk factors during follow-up, the HR of dementia in hypertensive versus non-hypertensive participants was 1.8 at age <55 years compared with 1.0 at age 70+ years. Parallel results were observed for diabetes (HR 3.4 in <55, 2.0 in >or=70), smoking (4.8 in <55, 0.5 in >or=70) and hypercholesterolaemia (HR 1.7 in <55, 0.9 in >or=70) CONCLUSION: In this prospective study, smoking, hypertension and diabetes were strongly associated with subsequent risk of hospitalisation with dementia, particularly in middle-aged individuals. Our results emphasise the importance of early lifestyle modification and risk factor treatment to prevent dementia.

HbA 1c as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA(1c), a measure of glycaemia control, and HF risk. METHODS: We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). RESULTS: In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p<0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11-1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11-1.29). CONCLUSIONS/INTERPRETATIONS: These data suggest HbA(1c) is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.

Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes.

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease (CVD). Translating these advances to simple and applicable public health measures must be adopted as a goal worldwide. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. The 2004 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on 'Definition and Classification of Chronic Kidney Disease' represented an important endorsement of the Kidney Disease Outcome Quality Initiative definition and classification of CKD by the international community. The 2006 KDIGO Controversies Conference on CKD was convened to consider six major topics: (1) CKD classification, (2) CKD screening and surveillance, (3) public policy for CKD, (4) CVD and CVD risk factors as risk factors for development and progression of CKD, (5) association of CKD with chronic infections, and (6) association of CKD with cancer. This report contains the recommendations from the meeting. It has been reviewed by the conference participants and approved as position statement by the KDIGO Board of Directors. KDIGO will work in collaboration with international and national public health organizations to facilitate implementation of these recommendations.

Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans.

BACKGROUND: The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher Lp(a) levels in African populations compared with non-African populations is unknown. OBJECTIVE: To evaluate the association between LPA sequence variations and Lp(a) in European Americans and African Americans and to determine the extent to which LPA sequence variations can account for between-population variations in Lp(a). METHODS: Serum Lp(a) and isoform measurements were examined in 534 European Americans and 249 African Americans from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study. In addition, 12 LPA variants were genotyped, including 8 previously reported LPA variants with a frequency of >2% in European Americans or African Americans, and four new variants. RESULTS: Isoform-adjusted Lp(a) level was 2.23-fold higher among African Americans. Three single-nucleotide polymorphisms (SNPs) were independently associated with Lp(a) level (p<0.02 in both populations). The Lp(a)-increasing SNP (G-21A, which increases promoter activity) was more common in African Americans, whereas the Lp(a)-lowering SNPs (T3888P and G+1/inKIV-8A, which inhibit Lp(a) assembly) were more common in European Americans, but all had a frequency of <20% in one or both populations. Together, they reduced the isoform-adjusted African American Lp(a) increase from 2.23 to 1.37-fold(a 60% reduction) and the between-population Lp(a) variance from 5.5% to 0.5%. CONCLUSIONS: Multiple low-prevalence alleles in LPA can account for the large between-population difference in serum Lp(a) levels between European Americans and African Americans.

Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study.

Elevated bone mineral parameters have been associated with mortality in dialysis patients. There are conflicting data about calcium, parathyroid hormone (PTH), and mortality and few data about changes in bone mineral parameters over time. We conducted a prospective cohort study of 1007 incident hemodialysis and peritoneal dialysis patients. We examined longitudinal changes in bone mineral parameters and whether their associations with mortality were independent of time on dialysis, inflammation, and comorbidity. Serum calcium, phosphate, and calcium-phosphate product (CaP) increased in these patients between baseline and 6 months (P<0.001) and then remained stable. Serum PTH decreased over the first year (P<0.001). In Cox proportional hazards models adjusting for inflammation, comorbidity, and other confounders, the highest quartile of phosphate was associated with a hazard ratio (HR) of 1.57 (1.07-2.30) using both baseline and time-dependent values. The highest quartiles of calcium, CaP, and PTH were associated with mortality in time-dependent models but not in those using baseline values. The lowest quartile of PTH was associated with an HR of 0.65 (0.44-0.98) in the time-dependent model with 6-month lag analysis. We conclude that high levels of phosphate both at baseline and over follow-up are associated with mortality in incident dialysis patients. High levels of calcium, CaP, and PTH are associated with mortality immediately preceding an event. Promising new interventions need to be rigorously tested in clinical trials for their ability to achieve normalization of bone mineral parameters and reduce deaths of dialysis patients.

Stability of haemoglobin A1c (HbA1c) measurements from frozen whole blood samples stored for over a decade.

OBJECTIVE: Haemoglobin A1c (HbA1c), a measure of long-term glycaemic control, is at the centre of the clinical management of diabetes mellitus. However, the reproducibility of HbA1c measurements from whole blood samples which have been in long-term storage is unknown. We undertook this study to assess the reproducibility of HbA1c measurements from whole blood samples that had been in storage at -70 degrees C for over a decade. RESEARCH DESIGN AND METHODS: Three hundred and thirty-six samples of frozen whole blood from the Atherosclerosis Risk in Communities (ARIC) Study, stored at -70 degrees C for 11-14 years assayed for HbA1c using a dedicated ion-exchange HPLC assay (Tosoh A1c 2.2 Plus HPLC) were compared with measurements on these same samples conducted prior to storage (in 1990-92) using a Diamat (Bio-Rad) HPLC instrument. RESULTS: HbA1c measurements from long-term stored samples were strongly correlated with values obtained prior to long-term storage (r=0.97). The difference between HbA1c from long- and short-term stored samples had a mean of 0.35% HbA1c (sd=0.35) and a CV of 5.8%, which was approximately three times that of duplicate assays (CV 1.3 to 2.5%). CONCLUSIONS: These data demonstrate that highly correlated but more variable and slightly higher HbA1c results were obtained from frozen whole blood samples that have been in storage for more than a decade. This highly reproducible assay performance would lead to comparable ranking of individuals and unbiased estimates of relative risks and odds ratios in epidemiological studies (case-control and cohort designs), but results should be realigned when the absolute value is of interest. These results have important implications for epidemiological studies and clinical trials which have stored whole blood specimens.

Undertreatment of hyperlipidemia in a cohort of United States kidney dialysis patients.

BACKGROUND: Application of national guidelines regarding cardiovascular disease risk reduction to kidney dialysis patients is complicated by the conflicting observations that dialysis patients have a high risk of atherosclerotic cardiovascular disease (ASCVD), but dialysis patients with higher serum cholesterol have lower mortality rates. Actual treatment patterns of hyperlipidemia are not well studied. METHODS: We assessed the prevalence, treatment and control of hyperlipidemia in this high-risk patient population from 1995 - 1998. We measured low-density lipoprotein cholesterol, treatment with a lipid-lowering agent, and prevalence of hyperlipidemia as defined by the National Cholesterol Education Program (NCEP), Adult Treatment Panel (ATP) II guidelines in 812 incident hemodialysis (HD), and peritoneal dialysis (PD) patients from dialysis clinics in 19 states throughout the United States. RESULTS: Hyperlipidemia was present in 40% of HD and 62% of PD patients. Among subjects with hyperlipidemia, 67% of HD and 63% of PD patients were untreated and only 22% of HD and 14% of PD patients were treated and controlled. Those who entered the study in 1997 or 1998, those with diabetes, males and Caucasians were more likely to be treated and controlled, whereas subjects on PD and those with ASCVD were less likely to be treated and controlled. CONCLUSION: These data suggest that high rates of undertreatment exist in the United States ESRD dialysis population. Whether improved rates of treatment will result in decreased cardiovascular disease events needs to be tested in randomized clinical trials.

Timing of nephrologist referral and arteriovenous access use: the CHOICE Study.

Recent clinical practice guidelines recommend the creation of an arteriovenous (AV) vascular access (ie, native fistula or synthetic graft) before the start of chronic hemodialysis therapy to prevent the need for complication-prone dialysis catheters. We report on the association of referral to a nephrologist with duration of dialysis-catheter use and type of vascular access used in the first 6 months of hemodialysis therapy. The study population is a representative cohort of 356 patients with questionnaire, laboratory, and medical record data collected as part of the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Center Study. Patients who reported being seen by a nephrologist at least 1 month before starting hemodialysis therapy (75%) were more likely than those referred later to use an AV access at initiation (39% versus 10%; P < 0.001) and 6 months after starting hemodialysis therapy (74% versus 56%; P < 0.01). Patients referred within 1 month of initiating hemodialysis therapy used a dialysis catheter for a median of 202 days compared with 64, 67, and 19 days for patients referred 1 to 4, 4 to 12, and greater than 12 months before initiating hemodialysis therapy, respectively (P trend < 0.001). Patients referred at least 4 months before initiating hemodialysis therapy were more likely than patients referred later to use an AV fistula, rather than a synthetic graft, as their first AV access (45% versus 31%; P < 0.01). These associations remained after adjustment for age, sex, race, marital status, education, insurance coverage, comorbid disease status, albumin level, body mass index, and underlying renal diagnosis. These data show that late referral to a nephrologist substantially increases the likelihood of dialysis-catheter use at the initiation of hemodialysis therapy and is associated with prolonged catheter use. Regardless of the time of referral, only a minority of patients used an AV access at the initiation of treatment, and greater than 25% had not used an AV access 6 months after initiation. Thus, further efforts to improve both referral patterns and preparation for dialysis after referral are needed.

Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994).

BACKGROUND: The prevalence and incidence of end-stage renal disease in the United States are increasing, but milder renal disease is much more common and may often go undiagnosed and undertreated. METHODS: A cross-sectional study of a representative sample of the US population was conducted using 16 589 adult participants aged 17 years and older in the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988 to 1994. An elevated serum creatinine level was defined as 141 micromol/L or higher (>/=1.6 mg/dL) for men and 124 micromol/L or higher (>/=1.4 mg/dL) for women (>99th percentile for healthy young adults) and was the main outcome measure. RESULTS: Higher systolic and diastolic blood pressures, presence of hypertension, antihypertensive medication use, older age, and diabetes mellitus were all associated with higher serum creatinine levels. An estimated 3.0% (5.6 million) of the civilian, noninstitutionalized US population had elevated serum creatinine levels, 70% of whom were hypertensive. Among hypertensive individuals with an elevated serum creatinine level, 75% received treatment. However, only 11% of all individuals with hypertension had their blood pressure reduced to lower than 130/85 mm Hg (the Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommendation for hypertensive individuals with renal disease); 27% had a blood pressure lower than 140/90 mm Hg. Treated hypertensive individuals with an elevated creatinine level had a mean blood pressure of 147/77 mm Hg, 48% of whom were prescribed one antihypertensive medication. CONCLUSION: Elevated serum creatinine level, an indicator of chronic renal disease, is common and strongly related to inadequate treatment of high blood pressure.

Associations of tibia lead, DMSA-chelatable lead, and blood lead with measures of peripheral nervous system function in former organolead manufacturing workers.

BACKGROUND: The goals of the present study were to compare and contrast associations of blood lead, DMSA-chelatable lead, current tibia lead, and back-extrapolated "peak" tibia lead with four peripheral nervous system (PNS) sensory and motor function measures in older males with past exposure to organic and inorganic lead. METHODS: Data were collected from former organolead manufacturing workers with an average of 16 years since last occupational lead exposure. Current tibia lead levels were measured by (109)Cd x-ray fluorescence. Sensory pressure thresholds (index and pinky fingers) and pinch and grip strength were measured with the Pressure-Specified Sensory Device (PSSD). RESULTS: In adjusted analyses, none of the four lead biomarkers was associated with sensory pressure threshold of the index finger or pinch or grip strength. In contrast, all four biomarkers were associated (P < or = 0.10) with pressure threshold of the pinky finger. The final linear regression models accounted for a small proportion of the variance in the sensory (1-3%) and motor measures (10-21%). CONCLUSIONS: This study found no strong association between lead biomarkers and selected PNS sensory or motor function measures among former organolead manufacturing workers with no recent occupational exposure to lead. Previously reported CNS findings in this cohort suggest that the PNS may be less sensitive to the chronic toxic effects of lead in this dose range among adults. It is also possible that the PNS has a greater capacity for repair than does the CNS, or that the PNS measures were less sensitive for detection of lead-related health outcomes than were the CNS measures.

Relation between gender and vascular access complications in hemodialysis patients.

Native arteriovenous (AV) fistulae for hemodialysis vascular access are believed to be associated with fewer complications than synthetic polytetrafluoroethylene (PTFE) grafts. We conducted a study among patients in the Dialysis Morbidity and Mortality Study to compare risk factors for complications of AV fistulae and PTFE grafts in men and women and to examine the effect of age on vascular access complications. We analyzed data from 833 incident patients with end-stage renal disease who had a PTFE graft (n = 621) or AV fistula (n = 212) in use 1 month after starting hemodialysis therapy. Follow-up using inpatient and outpatient Medicare administrative data identified a 1.8-times greater risk for a subsequent vascular access procedure for PTFE grafts (0.71 procedures/access-year) than for AV fistulae (0.39 procedures/access-year). Men with grafts and women with grafts or fistulae had a greater risk for a first subsequent access procedure than did men with fistulae (0.79, 0.65, and 0.59 versus 0.33 procedures/access-year, respectively). After adjustment for age, race, presence of diabetes mellitus, and history of smoking, peripheral vascular disease, and cardiovascular disease, use of a PTFE graft compared with an AV fistula was associated with a greater risk for a first subsequent procedure in men (relative hazard, 2.2; 95% confidence interval [CI], 1.6 to 2.9), but not in women (relative hazard, 1.0; 95% CI, 0.7 to 1.4). The excess risk associated with a PTFE graft compared with an AV fistula was limited to men in the lower three quartiles of age (ie,