Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease.

BACKGROUND: Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD. METHODS: We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors. RESULTS: In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08-1.40]}, QRS [OR 1.28 (95% CI 1.16-1.42)] and QTc [OR 1.94 (95% CI 1.50-2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06-1.16)] and QTc [OR 1.82 (95% CI 1.58-2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters. CONCLUSIONS: hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.

Effect of Anti-Hypertensive Medication History on Arteriovenous Fistula Maturation Outcomes.

BACKGROUND: The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, approximately half of AVFs fail to mature. The use of angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) exerts favorable endothelial effects and may promote AVF maturation. We tested associations of ACE-I and ARBs, CCBs, beta-blockers, and diuretics with the maturation of newly created AVFs. METHODS: We evaluated 602 participants from the Hemodialysis Fistula Maturation Study, a multi-center, prospective cohort study of AVF maturation. We ascertained the use of each medication class within 45 days of AVF creation surgery. We defined maturation outcomes by clinical use within 9 months of surgery or 4 weeks of initiating hemodialysis. RESULTS: Unassisted AVF maturation failure without intervention occurred in 54.0% of participants, and overall AVF maturation failure (with or without intervention) occurred in 30.1%. After covariate adjustment, CCB use was associated with a 25% lower risk of overall AVF maturation failure (95% CI 3%-41% lower) but a non-significant 10% lower risk of unassisted maturation failure (95% CI 23% lower to 5% higher). ACE-I/ARB, beta-blocker, and diuretic use was not significantly associated with AVF maturation outcomes. None of the antihypertensive medication classes were associated with changes in AVF diameter or blood flow over 6 weeks following surgery. CONCLUSIONS: CCB use may be associated with a lower risk of overall AVF maturation failure. Further studies are needed to determine whether CCBs might play a causal role in improving AVF maturation outcomes.

Racial and ethnic differences in kidney function decline among persons without chronic kidney disease.

Whether the rate of kidney function decline before the onset of CKD differs among racial and ethnic groups remains unclear. Here, we evaluated kidney function decline and incident CKD among white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA) during 5 years of follow-up. We estimated GFR using both cystatin C (eGFRcys) and creatinine (eGFRcreat). The definition of incident CKD required eGFRcys <60 ml/min per 1.73 m(2) and a decline in eGFRcys ≥1 ml/min per year. Among participants with eGFRcreat >60 ml/min per 1.73 m(2) at baseline, blacks had a significantly higher rate of kidney function decline than whites (0.31 ml/min per 1.73 m(2)/yr faster on average, P=0.001), even after adjusting for multiple potential confounders. Among Hispanics, Dominicans and Puerto Ricans had faster rates of decline than whites (0.55 and 0.47 ml/min per 1.73 m(2)/yr faster, respectively). Mexicans, South Americans, or other Hispanics had similar rates of decline compared to whites. We did not detect significant differences in the rates of kidney function decline among Chinese and white participants. Among those with normal or near-normal kidney function at baseline, blacks and Hispanics had the highest rates of incident CKD during follow-up. Adjustment for comorbidities attenuated some of these differences. In conclusion, the average rate of kidney function decline before the onset of CKD differs among racial and ethnic groups. Traditional risk factors do not explain these differences fully, highlighting the need to explore these disparities.

Kidney function decline in the elderly: impact of lipoprotein-associated phospholipase A(2).

BACKGROUND: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied. METHODS: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≥3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (≥60 ml/min/1.73 m(2)). RESULTS: Mean age was 72 ± 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, ß -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline. CONCLUSION: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.

Relations of Postload and Fasting Glucose With Incident Cardiovascular Disease and Mortality Late in Life: The Cardiovascular Health Study.

BACKGROUND: Older adults have a high prevalence of postload hyperglycemia. Postload glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in the oldest old are sparse. METHODS: Fasting and 2-hour postload glucose were measured in community-dwelling older adults, mean age 78, at the 1996-1997 follow-up visit of the Cardiovascular Health Study. We evaluated their associations with atherosclerotic CVD (ASCVD) and mortality using standard Cox regression and competing-risks analyses and assessed improvement in prediction-model discrimination with the c-statistic. RESULTS: Among 2,394 participants without treated diabetes and available data on glycemic measures, there were 579 ASCVD events and 1,698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with ASCVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and all-cause mortality (HR 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with both outcomes were abolished, but those for postload glucose were largely unchanged. Consistent findings were observed for ASCVD in competing-risks models. CONCLUSION: In adults surviving to advanced old age, postload glucose was associated with ASCVD and mortality independently of fasting glucose, but fasting glucose was not associated with these outcomes independently of postload glucose. These findings affirm the robust association of postload glucose with ASCVD and death late in life.

Association of subcutaneous and visceral adiposity with albuminuria: the Framingham Heart Study.

Microalbuminuria is a common condition associated with increased incidence of cardiovascular events and mortality. Abdominal obesity is associated with microalbuminuria, but studies linking visceral adipose tissue (VAT) and microalbuminuria are limited. Our objective was to determine the associations of albuminuria with VAT and subcutaneous adipose tissue (SAT). We performed a cross-sectional study in the Framingham Multi-Detector Computed Tomography (MDCT) cohort (n = 3099, 48.2% women, mean age 53 years). VAT and SAT volumes were measured using computed tomography. Urinary albumin-to-creatinine ratio (UACR) was calculated from spot urine samples. Microalbuminuria was defined as a UACR >25 mg/g in women or >17 mg/g in men. Overall, 7.9% (n = 244) of the sample had microalbuminuria. Among men, VAT (odds ratio (OR) 1.48 per s.d., P < 0.0001) and SAT (OR 1.37 per s.d., P = 0.0002) were associated with microalbuminuria in minimally adjusted models, which remained significant after multivariable adjustment (VAT OR 1.34 per s.d., P = 0.001; SAT OR 1.28 per s.d., P = 0.005). Additionally, when considered jointly, VAT (P = 0.002) but not SAT (P = 0.2) was associated with microalbuminuria. In women, VAT was associated with microalbuminuria after minimal adjustment (OR 1.28, P = 0.01), but not after multivariable adjustment (OR 1.03, P = 0.8). In multivariable models in women, SAT was associated with a decreased odds of having microalbuminuria (OR 0.75 per s.d., P = 0.03). In conclusion, VAT is associated with microalbuminuria in men but not women. Albuminuria may be a manifestation of visceral adiposity.