Aspirin for Primary and Secondary Prevention of Mortality, Cardiovascular Disease, and Kidney Failure in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale and Objective: Chronic kidney disease is a risk enhancing factor for cardiovascular disease (CVD) and mortality, and the role of aspirin use is unclear in this population. We investigated the risk and benefits of aspirin use in primary and secondary prevention of CVD in the Chronic Renal Insufficiency Cohort Study. Study Design: Prospective observational cohort. Setting & Participants: 3,664 Chronic Renal Insufficiency Cohort participants. Exposure: Aspirin use in patients with and without preexisting CVD. Outcomes: Mortality, composite and individual CVD events (myocardial infarction, stroke, and peripheral arterial disease), kidney failure (dialysis and transplant), and major bleeding. Analytical Approach: Intention-to-treat analysis and multivariable Cox proportional hazards model to examine associations of time varying aspirin use. Results: The primary prevention group was composed of 2,578 (70.3%) individuals. Mean age was 57 ± 11 years, 46% women, 42% Black, and 47% had diabetes. The mean estimated glomerular filtration rate was 45 mL/min/1.73 m2. Median follow-up was 11.5 (IQR, 7.4-13) years. Aspirin was not associated with all-cause mortality in those without preexisting cardiovascular disease (CVD) (HR, 0.84; 95% CI, 0.7-1.01; P = 0.06) or those with CVD (HR, 0.88; 95% CI, 0.77-1.02, P = 0.08). Aspirin was not associated with a reduction of the CVD composite in primary prevention (HR, 0.97; 95% CI, 0.77-1.23; P = 0.79) and in secondary prevention because the original study design was not meant to study the effects of aspirin. Limitations: This is not a randomized controlled trial, and therefore, causality cannot be determined. Conclusions: Aspirin use in chronic kidney disease patients was not associated with reduction in primary or secondary CVD events, progression to kidney failure, or major bleeding.

Health-Related Quality of Life, Depressive Symptoms, and Kidney Transplant Access in Advanced CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Among individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list. STUDY DESIGN: Prospective cohort study. SETTING & POPULATION: 1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m2 at study entry or during follow-up. EXPOSURES: HRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory. OUTCOMES: Time to kidney transplant wait-listing and time to pre-emptive wait-listing. ANALYTIC APPROACH: Time-to-event analysis using Cox proportional hazards regression. RESULTS: During a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P < 0.001) and Effects scales (wait-listing aHR, 0.74; 95% CI, 0.59-0.92; P = 0.007). Participants with fewer depressive symptoms (ie, Beck Depression Inventory score < 14) had lower wait-listing rates than those with more depressive symptoms (aHR, 0.81; 95% CI, 0.66-0.99; P = 0.04). Participants with lower Burden and Effects scale scores and those with higher Symptoms and PCS scores had higher pre-emptive wait-listing rates (aHR in highest tertile of PCS relative to lowest tertile, 1.58; 95% CI, 1.12-2.23; P = 0.01). LIMITATIONS: Unmeasured confounders. CONCLUSIONS: Self-reported health in late-stage CKD may influence the timing of kidney transplantation.

Peripheral arterial disease, prevalence and cumulative risk factor profile analysis.

BACKGROUND: The primary aim of the present study was to determine the cumulative effect of a set of peripheral artery disease (PAD) risk factors among age, gender and race/ethnicity groups in the United States. METHODS: We examined data from a nationally representative sample of the US population (National Health and Nutrition Examination Survey [NHANES], 1999-2004). A total of 7058 subjects 40 years or older that completed the interview, medical examination and had ankle-brachial index (ABI) measurements were included in this study. RESULTS: The age- and sex-standardized prevalence of PAD was 4.6 % (standard error [SE] 0.3%).The highest prevalence of PAD was observed among elderly, non-Hispanic Blacks and women. In a multivariable age-, gender- and race/ethnicity-adjusted model hypertension, diabetes, chronic kidney disease, and smoking were retained as PAD risk factors (p ≤ 0.05 for each). The odds of PAD increased with each additional risk factor present from a non-significant 1.5-fold increase (O.R 1.5, 95% confidence interval [CI] 0.9-2.6) in the presence of one risk factor, to more than ten-fold (OR 10.2, 95% CI 6.4-16.3) in the presence of three or more risk factors. In stratified analysis, non-Hispanic Blacks (OR 14.7, 95% CI 2.1-104.1) and women (OR 18.6, 95% CI 7.1-48.7) were particularly sensitive to this cumulative effect. CONCLUSION: In a large nationally representative sample, an aggregate set of risk factors that included diabetes mellitus, chronic kidney disease, hypertension and smoking significantly increase the likelihood of prevalent PAD. A cumulative risk factor analysis highlights important susceptibility differences among different population groups and provides additional evidence to redefine screening strategies in PAD.

Mean platelet volume and prevalence of peripheral artery disease, the National Health and Nutrition Examination Survey, 1999-2004.

OBJECTIVES: We sought to determine whether mean platelet volume (MPV) is associated with the prevalence of peripheral artery disease (PAD). BACKGROUND: Platelets play a pivotal role in the pathogenesis of atherosclerosis and PAD. MPV, a measure of platelet size available in every blood count, is increasingly recognized as an important marker of platelet activity. METHODS: We analyzed data from 6354 participants aged 40 years and older from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. PAD was defined as an ankle brachial index ≤ 0.90 in either leg. Odds ratios and 95% confidence intervals were estimated by logistic regression. RESULTS: The prevalence of PAD in the cohort was 5.7%. MPV was significantly associated with PAD prevalence (tertile 1 - 4.4%, tertile 2 - 6.1%, tertile 3 - 7.0%, P for trend=0.003). After adjustment for age, sex, and race, the odds ratio of PAD comparing the highest tertile to the lowest tertile was 1.57 (95% confidence interval 1.15-2.13). After further adjustment for smoking status, hypertension, hypercholesterolemia, diabetes, glomerular filtration rate, body mass index, and platelet count the corresponding odds ratio was 1.58 (95% confidence interval 1.14-2.19). The addition of triglycerides, hemoglobin A1c, and C-reactive protein did not affect the results. The significant association between MPV and PAD was unchanged when MPV was used as a continuous variable. CONCLUSIONS: Mean platelet volume is independently associated with PAD. These findings support the hypothesis that platelet size is an independent predictor of increased risk for PAD.