Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality.

BACKGROUND: Previous studies have identified multiple risk factors that are associated with total cardiac mortality. Nevertheless, identifying specific factors that distinguish patients at risk of arrhythmic death versus heart failure could better target patients likely to benefit from implantable cardiac defibrillators, which have no impact on nonsudden cardiac death. METHODS AND RESULTS: We performed a pilot competing risks analysis of the National Institutes of Health-sponsored PAREPET trial (Prediction of Arrhythmic Events with Positron Emission Tomography). Death from cardiac causes was ascertained in subjects with ischemic cardiomyopathy (n=204) eligible for an implantable cardiac defibrillator for the primary prevention of sudden cardiac arrest after baseline clinical evaluation and imaging at enrollment (positron emission tomography and 2-dimensional echo). Mean age was 67±11 years with an ejection fraction of 27±9%, and 90% were men. During 4.1 years of follow-up, there were 33 sudden cardiac arrests (arrhythmic death or implantable cardiac defibrillator discharge for ventricular fibrillation or ventricular tachycardia >240 bpm) and 36 nonsudden cardiac deaths. Sudden cardiac arrest was correlated with a greater volume of denervated myocardium (defect of the positron emission tomography norepinephrine analog 11C-hydroxyephedrine), lack of angiotensin inhibition therapy, elevated B-type natriuretic peptide, and larger left ventricular end-diastolic volume index. In contrast, nonsudden cardiac death was associated with a higher resting heart rate, older age, elevated creatinine, larger left atrial volume index, and larger left ventricular end-diastolic volume index. CONCLUSIONS: Distinct clinical, laboratory, and imaging variables are associated with cause-specific cardiac mortality in primary-prevention candidates with ischemic cardiomyopathy. If prospectively validated, these multivariable associations may help target specific therapies to those at the greatest risk of sudden and nonsudden cardiac death. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01400334.

Progression of kidney disease in elderly stage 3 and 4 chronic kidney disease patients.

PURPOSE: The prevalence of chronic kidney disease (CKD) has been rising steadily in the elderly population. We studied the rate of progression of CKD in this population and the factors associated with progression of CKD to better identify patients who are likely to progress to ESRD. METHODS: This was an observational study including 4562 patients older than 65 years with two outpatient estimated glomerular filtration rates (eGFRs) of <60 ml/min/1.73 m2, at least 90 days apart with no intervening eGFR >60 ml/min/1.73 m2 (March 1, 2001, and March 31, 2008) at VA healthcare facilities. Patients with eGFR <15 ml/min/1.73 m2 were excluded. Annual rate of decline of eGFR was studied and categorized as <1 ml/min/1.73 m2, 1-4 ml/min/1.73 m2, and >4 ml/min/1.73 m2. RESULTS: Mean age of the study participants was 77.2 years. 24.3% were diabetics. 4.3% had proteinuria. In univariate comparison of different rates of progression, 54.2% patients had an annual rate of progression of <1 ml/min/1.73 m2. Multivariable mixed model analyses revealed that increasing age, body mass index, presence of cardiovascular disease, diabetes mellitus, and proteinuria were associated with significantly increased rate of progression of CKD. Serum albumin and hemoglobin level were inversely associated with progression of CKD. CONCLUSIONS: CKD progresses at a slower rate in the elderly population. We have identified risk factors associated with an increased risk of progression of CKD in the elderly. This may help to improve health care planning and resource utilization.

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease.

BACKGROUND: Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. METHODS: Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. RESULTS: A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs. CONCLUSIONS: Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

Prevalence of various comorbidities among veterans with chronic kidney disease and its comparison with other datasets.

Chronic kidney disease (CKD) has a complicated interrelationship with various comorbidities. The purpose of this study was to describe the prevalence of various comorbidities among veterans with CKD and compare it with other datasets like Kidney Early Evaluation Program (KEEP), National Health and Nutrition Examination Survey (NHANES) and Medicare. Patients who had at least one outpatient visit in year 2007 (1 January 2007 to 31 December 2007) were included in the study (n = 75,787). Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease (MDRD) study equation. CKD prevalence was calculated based on one or two serum creatinine values at least 3 months apart. Demographic data were obtained including age, gender, race, weight, height and body mass index (BMI). The prevalence of various comorbidities was also collected based on ICD 9 codes from the problem list. The prevalence of CKD among veterans was 47.3%, much higher than estimated in the US population. Patients with CKD were more likely to have any vascular disease (36.89% vs. 14.87%), diabetes (34.18% vs. 17.83%), hypertension (86.65% vs. 57.56%), and cancer (18.69% vs. 9.23%). Irrespective of age, the prevalence of vascular disease was much higher among veterans with CKD. The prevalence of coronary artery disease, peripheral vascular disease, and cancer was much higher among elderly veterans with CKD as compared to other datasets. CKD is a growing endemic associated with a high frequency of concomitant chronic illnesses. Public health resources should be applied for early recognition and risk modification of CKD.

Renin-Angiotensin-Aldosterone System Blockers in Elderly Adults with Chronic Kidney Disease without Diabetes Mellitus or Proteinuria.

OBJECTIVES: To compare the effect of renin-angiotensin-aldosterone system (RAAS) blockers with that of other antihypertensive agents on outcomes in a cohort of elderly veterans with incident chronic kidney disease (CKD) without diabetes mellitus or proteinuria. DESIGN: Retrospective cohort study. SETTING: Veterans Affairs (VA) Upstate New York Healthcare System. PARTICIPANTS: All participants were seen in primary care clinic in Veterans Integrated Service Network 2, which comprises five VA medical centers and 29 community-based outpatient clinics, from April 2001 to April 2008. Veterans with incident CKD who were taking antihypertensive medications and did not have proteinuria or diabetes mellitus on the date of onset of CKD were selected from this population. MEASUREMENTS: The outcome variables studied were progression of kidney disease (doubling of serum creatinine level or Stage 5 CKD (estimated glomerular filtration rate <15 mL/min per 1.73 m2 )), all-cause mortality, and combined outcome. RESULTS: Analysis included 2,474 participants, 47.9% of whom were taking RAAS blockers at baseline and the rest other antihypertensives. Time-varying Cox proportional hazards analyses did not reveal a statistically significant difference in primary combined outcome in participants taking RAAS blockers and those taking other antihypertensives (hazard ratio = 1.09, 95% confidence interval = 0.93-1.27). There was also no significant effect on individual outcomes (death or progression of kidney disease). CONCLUSION: Use of RAAS blockers was not associated with less hazard of combined and individual outcomes (doubling of serum creatinine, Stage 5 CKD, death) in elderly veterans with incident CKD without diabetes mellitus or proteinuria.

Elevated systolic blood pressure is associated with increased incidence of chronic kidney disease but not mortality in elderly veterans.

The optimal blood pressure to prevent development of chronic kidney disease (CKD) and mortality in the elderly is unclear. Our objective was to determine the effect of differing levels of blood pressure on incidence of CKD and mortality in elderly veterans. This retrospective cohort study included 15,221 individuals ≥70 years of age without CKD (outpatient estimated glomular filtration rate >60 mL/min/1.73 m(2)) seen in the primary care clinic in the Veterans Affairs Health Care Upstate New York with Veterans Integrated Service Network 2 between 2001 and 2008. To examine the association of explanatory variables on hazard ratios for outcomes of interest, incident CKD, and death, competing risk analysis (with death as competing risk) was used for the analysis of incident CKD outcome, and time-dependent Cox model with CKD as the time-dependent covariate was used for the analysis of death outcome. The incidence of CKD was 16% over a median follow-up of 19 quarters. Compared with reference of systolic blood pressure of 130-139 mm Hg, there was an increased hazard of development of CKD with systolic blood pressure of 140-149 mm Hg or higher. As compared with a reference range of 130-139 mm Hg systolic blood pressure, the relative risk of mortality was higher in the range of 120-129 mm Hg systolic or less. The optimal achieved systolic blood pressure in elderly patients to prevent the development of CKD was <140 mm Hg. However, lowering the systolic blood pressure below 130 mm Hg was associated with increased mortality.

Maternal and infant factors associated with excess kindergarten costs.

OBJECTIVE: To estimate the excess educational costs at kindergarten from infant and maternal factors that are reported routinely at birth. METHODS: Birth and school records were analyzed for all children who were born in Florida between September 1, 1990, and August 31, 1991, and entered kindergarten from 1996 through 1999 (N = 120,554). Outcome measure was cost to state, derived from base allocation for students in regular classrooms plus multiplier weights for those who were assigned to 8 mutually exclusive special education categories or who repeated kindergarten. RESULTS: More than one quarter of the study cohort was found to be assigned to special education classes at kindergarten. Regression model estimates indicated that children who were born at <1000 g (n = 380) generated 71% higher costs in kindergarten than children who were born at >or=2500 g. Children who were born at 1000 to 1499 g (n = 839) generated 49% higher costs. Other birth conditions, independent of birth weight, were associated with higher kindergarten costs: family poverty (31%), congenital anomalies (29%), maternal education less than high school (20%), and no prenatal care (14%). Because of their prevalence, family poverty and low maternal education accounted for >75% of excess kindergarten costs. If 9% of infants who weighed between 1500 and 2499 g (n = 1027) could be delivered at 2500 g, then the state of Florida potentially could save 1 million dollars in kindergarten costs. Savings of a similar magnitude might be achieved if 3% of mothers who left school without a diploma (n = 1528) were to graduate. CONCLUSIONS: Any policy recommendation aimed at reducing education costs in kindergarten must take into consideration 3 factors: the prevalence of risk conditions whose amelioration is desired, the potential cost savings associated with reducing those conditions, and the costs of amelioration. Projecting these costs from information that is available at birth can assist school districts and state agencies in allocating resources.