Coronary Artery Calcification and Risk of Cardiovascular Disease and Death Among Patients With Chronic Kidney Disease.

Importance: Coronary artery calcification (CAC) is highly prevalent in dialysis-naive patients with chronic kidney disease (CKD). However, there are sparse data on the association of CAC with subsequent risk of cardiovascular disease and all-cause mortality in this population. Objective: To study the prospective association of CAC with risk of cardiovascular disease and all-cause mortality among dialysis-naive patients with CKD. Design, Setting, and Participants: The prospective Chronic Renal Insufficiency Cohort study recruited adults with an estimated glomerular filtration rate of 20 to 70 mL/min/1.73 m2 from 7 clinical centers in the United States. There were 1541 participants without cardiovascular disease at baseline who had CAC scores. Exposures: Coronary artery calcification was assessed using electron-beam or multidetector computed tomography. Main Outcomes and Measures: Incidence of cardiovascular disease (including myocardial infarction, heart failure, and stroke) and all-cause mortality were reported every 6 months and confirmed by medical record adjudication. Results: During an average follow-up of 5.9 years in 1541 participants aged 21 to 74 years, there were 188 cardiovascular disease events (60 cases of myocardial infarction, 120 heart failures, and 27 strokes; patients may have had >1 event) and 137 all-cause deaths. In Cox proportional hazards models adjusted for age, sex, race, clinical site, education level, physical activity, total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, use of antihypertensive treatment, current cigarette smoking, diabetes status, body mass index, C-reactive protein level, hemoglobin A1c level, phosphorus level, troponin T level, log N-terminal pro-B-type natriuretic peptide level, fibroblast growth factor 23 level, estimated glomerular filtration rate, and proteinuria, the hazard ratios associated with per 1 SD log of CAC were 1.40 (95% CI, 1.16-1.69; P < .001) for cardiovascular disease, 1.44 (95% CI, 1.02-2.02; P = .04) for myocardial infarction, 1.39 (95% CI, 1.10-1.76; P = .006) for heart failure, and 1.19 (95% CI, 0.94-1.51; P = .15) for all-cause mortality. In addition, inclusion of CAC score led to an increase in the C statistic of 0.02 (95% CI, 0-0.09; P < .001) for predicting cardiovascular disease over use of all the above-mentioned established and novel cardiovascular disease risk factors. Conclusions and Relevance: Coronary artery calcification is independently and significantly related to the risks of cardiovascular disease, myocardial infarction, and heart failure in patients with CKD. In addition, CAC improves risk prediction for cardiovascular disease, myocardial infarction, and heart failure over use of established and novel cardiovascular disease risk factors among patients with CKD; however, the changes in the C statistic are small.

Edge control in a computer controlled optical surfacing process using a heterocercal tool influence function.

Edge effect is regarded as one of the most difficult technical issues in a computer controlled optical surfacing (CCOS) process. Traditional opticians have to even up the consequences of the two following cases. Operating CCOS in a large overhang condition affects the accuracy of material removal, while in a small overhang condition, it achieves a more accurate performance, but leaves a narrow rolled-up edge, which takes time and effort to remove. In order to control the edge residuals in the latter case, we present a new concept of the 'heterocercal' tool influence function (TIF). Generated from compound motion equipment, this type of TIF can 'transfer' the material removal from the inner place to the edge, meanwhile maintaining the high accuracy and efficiency of CCOS. We call it the 'heterocercal' TIF, because of the inspiration from the heterocercal tails of sharks, whose upper lobe provides most of the explosive power. The heterocercal TIF was theoretically analyzed, and physically realized in CCOS facilities. Experimental and simulation results showed good agreement. It enables significant control of the edge effect and convergence of entire surface errors in large tool-to-mirror size-ratio conditions. This improvement will largely help manufacturing efficiency in some extremely large optical system projects, like the tertiary mirror of the Thirty Meter Telescope.

Arterial stiffness, central pressures, and incident hospitalized heart failure in the chronic renal insufficiency cohort study.

BACKGROUND: Chronic kidney disease is associated with an increased risk of heart failure (HF). We aimed to evaluate the role of large artery stiffness, brachial, and central blood pressure as predictors of incident hospitalized HF in the Chronic Renal Insufficiency Cohort (CRIC), a multiethnic, multicenter prospective observational study of patients with chronic kidney disease. METHODS AND RESULTS: We studied 2602 participants who were free of HF at baseline. Carotid-femoral pulse wave velocity (CF-PWV; the gold standard index of large artery stiffness), brachial, and central pressures (estimated via radial tonometry and a generalized transfer function) were assessed at baseline. Participants were prospectively followed up to assess the development of new-onset hospitalized HF. During 3.5 years of follow-up, 154 participants had a first hospital admission for HF. CF-PWV was a significant independent predictor of incident hospitalized HF. When compared with the lowest tertile, the hazard ratios among subjects in the middle and top CF-PWV tertiles were 2.33 (95% confidence interval, 1.37-3.97; P=0.002) and 5.24 (95% confidence interval, 3.22-8.53; P<0.0001), respectively. After adjustment for multiple confounders, the hazard ratios for the middle and top CF-PWV tertiles were 1.95 (95% confidence interval, 0.92-4.13; P=0.079) and 3.01 (95% confidence interval, 1.45-6.26; P=0.003), respectively. Brachial systolic and pulse pressure were also independently associated with incident hospitalized HF, whereas central pressures were less consistently associated with this end point. The association between CF-PWV and incident HF persisted after adjustment for systolic blood pressure. CONCLUSIONS: Large artery stiffness is an independent predictor of incident HF in chronic kidney disease, an association with strong biological plausibility given the known effects of large artery stiffening of left ventricular pulsatile load.

Limited health literacy is associated with low glomerular filtration in the Chronic Renal Insufficiency Cohort (CRIC) study.

BACKGROUND: Low health literacy in the general population is associated with increased risk of death and hospitalization. The evaluation of health literacy in individuals with predialysis chronic kidney disease (CKD) is limited. METHODS: We conducted a cross-sectional study to evaluate the associations of limited health literacy with kidney function and cardiovascular disease (CVD) risk factors in 2,340 non-Hispanic (NH) Whites and Blacks aged 21 - 74 years with mild-to-moderate CKD. Limited health literacy was defined as a Short Test of Functional Health Literacy in Adults (STOFHLA) score ≤ 22. Outcomes evaluated included estimated glomerular filtration rate (eGFR), 24-hour urine protein excretion, and CVD risk factors. RESULTS: The prevalence of limited health literacy was 28% in NH-Blacks and 5% in NH-Whites. Compared with participants with adequate health literacy, those with limited health literacy were more likely to have lower eGFR (34 vs. 42 mL/min/1.73 m2); higher urine protein/24-hours (0.31 vs. 0.15 g); and higher self-reported CVD (61 vs. 37%); and were less likely to have BP < 130/80 mmHg (51 vs. 58%); p ≤ 0.01 for each comparison. After adjustment, limited health literacy was associated with self-reported CVD (OR 1.51, 95% CI 1.13 - 2.03) and lower eGFR (ß -2.47, p = 0.03). CONCLUSION: In this CKD cohort, limited health literacy was highly prevalent, especially among NH-Blacks, and it was associated with lower eGFR and a less favorable CVD risk factor profile. Further studies are needed to better understand these associations and inform the development of health literacy interventions among individuals with CKD.

Approximation of normalized point source sensitivity using power spectral density and slopes of wavefront aberration.

We have investigated two approximation methods for estimating the normalized point source sensitivity (PSSN), which is a recently developed optical performance metric for telescopes. One is an approximation based on the power spectral density (PSD) of the wavefront error. The other is the root-square-sum of the wavefront slope. We call these approximations ß approximation and SlopeRMS approximation, respectively. Our analysis shows that for the Thirty Meter Telescope (TMT), the uncertainty of the ß approximation is less than 1×10(-3) if the PSSN is better than 0.95, assuming the input PSD estimation is accurate. In addition, we find that the SlopeRMS approximation is a simple method for estimating the worst-case PSSN value in the specific situation when the PSSN is dominated by low-frequency aberrations. Therefore, the SlopeRMS approximation is expected to be useful for specifying a mirror surface for mirror vendors. Accordingly, TMT has a plan to adopt the SlopeRMS approximation for its M2 and M3 polishing specification.

Factors associated with depressive symptoms and use of antidepressant medications among participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies.

BACKGROUND: Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied. STUDY DESIGN: Cross-sectional analysis. SETTINGS & PARTICIPANTS: Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at 7 centers in 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois in 2005-2008. MEASUREMENT: Depressive symptoms measured by Beck Depression Inventory (BDI). PREDICTORS: Demographic and clinical factors. OUTCOMES: Elevated depressive symptoms (BDI score ≥11) and antidepressant medication use. RESULTS: Of 3,853 participants, 27.4% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 31.0% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 23.6% for participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and 33.8% of those with eGFR <30 mL/min/1.73 m(2). Lower eGFR (OR per 10-mL/min/1.73 m(2) decrease, 1.10; 95% CI, 1.04-1.17), and non-Hispanic black race (OR, 1.42; 95% CI, 1.16-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, whereas female sex was associated with greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher urine albumin levels were associated with decreased odds of antidepressant use (P < 0.05 for each). LIMITATIONS: Absence of clinical diagnosis of depression and use of nonpharmacologic treatments. CONCLUSIONS: Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. Individuals of racial and ethnic minority background and with more advanced CKD had a greater burden of elevated depressive symptoms and lower use of antidepressant medications.

Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: A low rate of blood pressure control has been reported in patients with chronic kidney disease (CKD). These data were derived from population-based samples with a low rate of CKD awareness. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: Data from the baseline visit of the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,612) were analyzed. Participants with an estimated glomerular filtration rate of 20-70 mL/min/1.73 m(2) were identified from physician offices and review of laboratory databases. OUTCOMES: Prevalence and awareness of hypertension, treatment patterns, control rates, and factors associated with hypertension control. MEASUREMENTS: Following a standardized protocol, blood pressure was measured 3 times by trained staff, and hypertension was defined as systolic blood pressure > or =140 mm Hg and/or diastolic blood pressure > or =90 mm Hg and/or self-reported antihypertensive medication use. Patients' awareness and treatment of hypertension were defined using self-report, and 2 levels of hypertension control were evaluated: systolic/diastolic blood pressure <140/90 and <130/80 mm Hg. RESULTS: The prevalence of hypertension was 85.7%, and 98.9% of CRIC participants were aware of this diagnosis and 98.3% were treated with medications, whereas 67.1% and 46.1% had hypertension controlled to <140/90 and <130/80 mm Hg, respectively. Of CRIC participants with hypertension, 15%, 25%, 26%, and 32% were using 1, 2, 3, and > or =4 antihypertensive medications, respectively. After multivariable adjustment, older patients, blacks, and those with higher urinary albumin excretion were less likely, whereas participants using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were more likely to have controlled their hypertension to <140/90 and <130/80 mm Hg. LIMITATIONS: Data were derived from a single study visit. CONCLUSIONS: Despite almost universal hypertension awareness and treatment in this cohort of patients with CKD, rates of hypertension control were suboptimal.

Symptomatic hyponatremia during glomerular filtration rate testing.

Hyponatremia affects nearly one in five of all hospitalized patients. Severe hyponatremia is associated with significant morbidity and mortality, and is therefore important to recognize. Prior reports have linked duloxetine with hyponatremia, but it is uncommon. In this case report, we describe a research subject taking duloxetine who developed severe symptomatic hyponatremia during glomerular filtration rate testing despite having undergone such testing uneventfully in the past.

A randomized, double-blind, placebo-controlled trial of casein protein hydrolysate (C12 peptide) in human essential hypertension.

BACKGROUND: Many patients seek complementary medicine treatments like neutraceuticals for common conditions such as hypertension. METHODS: We conducted a placebo-controlled prospective randomized crossover study in 10 hypertensive subjects to determine whether a single dose of a hydrolysate of bovine milk protein (designated C12 peptide; low and high dose), either alone or combined with alginic acid (low and high dose), reduced daytime blood pressure (BP), as determined by ambulatory BP monitoring. RESULTS: Within the five treatment regimens a significant reduction of 9.2 +/- 3.2 mm Hg in systolic BP at h 6 compared with h 2 occurred on the higher dose of alginic acid (1754 mg) combined with C12 (P = .02). The C12 peptide with the higher dose of alginic acid also showed a significant reduction of 6.0 +/- 2.0 mm Hg in diastolic BP at h 6 compared with h 2 (P = .015). CONCLUSIONS: These preliminary data are encouraging and deserve testing in a larger and longer treatment trial.

Thrombomodulin distribution during murine development.

Thrombomodulin is a transmembrane glycoprotein involved in the regulation of clot formation. Previous work has shown that in the adult mouse, thrombomodulin expression is primarily located on the luminal surface of endothelial cells; whereas during development, thrombomodulin has been localized to the placental parietal endoderm, the neuroepithelium, head mesenchyme, lung bud, and atrium of Day 10.5 post coitum embryos. We examined the expression of thrombomodulin in the adult mouse and throughout murine development from Day 7.5 to Day. 18.5 post coitum. The high expression of thrombomodulin in the lung bud, developing gonads, leptomeninges, and the parietal endoderm in comparison to the expression levels in the adult organs suggest that thrombomodulin may play an important role in development.The submitted manuscript has been authored by a contractor of the U.S. Government under contract No. DE-AC05-840R21400. Accordingly, the U.S. Government retains nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for US Government purposes.