Stephen F. Derose

Association between Serum Lipids and Survival in Hemodialysis Patients and Impact of Race

Despite the enormous cardiovascular disease epidemic among maintenance hemodialysis (MHD) patients, total hypercholesterolemia seems paradoxically to be associated with better survival. It was hypothesized that similar paradoxic associations also exist for serum LDL, HDL, and triglycerides. A 3-yr (July 2001 through June 2004) cohort of 15,859 MHD patients was studied in the United States from DaVita dialysis clinics where lipid profile was measured in at least 50% of all outpatients during a given calendar quarter. Cox proportional hazard models were adjusted for case mix and surrogates of malnutrition-inflammation complex. Both total and LDL hypercholesterolemia showed a paradoxic association with better survival. Hypertriglyceridemia (>200 mg/dl) also showed a similar trend, but serum HDL cholesterol did not have any clear association with survival. The association between a low serum LDL <70 mg/dl, which was prevalent among almost 50% of all MHD patients, and a higher all-cause death risk was robust to multivariate adjustment. In the subgroup analyses, these paradoxic associations persisted among most subgroups, although they tended to be stronger among hypoalbuminemic (<3.8 mg/dl) patients and those with a lower dietary protein intake (<1 g/kg per d). However, in black patients, a high serum LDL (>100 mg/ml) was associated with adjusted cardiovascular death hazard ratio of 1.94 (95% confidence interval 1.12 to 2.38; P = 0.02). Despite inverse associations between hyperlipidemia and survival, black MHD patients with high LDL show almost two-fold increase in cardiovascular death risk. Although these associations may not be causal, they call into question whether specific subgroups of dialysis patients are better targets for cholesterol-lowering therapy.

Sleep Apnea in Early and Advanced Chronic Kidney Disease* Kaiser Permanente Southern California Cohort

BACKGROUND Sleep apnea (SA) has been reported to be highly prevalent in the dialysis population. The reported rates of SA in dialysis are severalfold greater than the 2 to 4% estimated in the general population. This study sought to determine whether an association exists between SA and early stages of chronic kidney disease (CKD) where SA may represent an important comorbidity and potential risk factor in kidney disease. METHODS Cross-sectional study of adults from an integrated health plan with documented serum creatinine levels in the period January 1, 2002, through December 31, 2004. SA diagnosis determined by International Classification of Diseases, ninth revision, coding for SA and Current Procedural Terminology coding for positive airway pressure devices. Kidney function was determined by the estimated glomerular filtration rate (eGFR). Logistic was regression used to estimate the relative risk for SA. RESULTS The overall prevalence of SA was 2.5% in the study population that included subjects with normal renal function and those with CKD. The odds ratios (ORs) for SA by eGFRs of 75 to 89, 60 to 74, 45 to 59, 30 to 44, and 15 to 29 mL/min per 1.73 m(2), respectively, compared to normal kidney function, after adjustment for age, sex, and number of visits, were as follows: 1.22 (95% confidence interval [CI], 1.18 to 1.25); 1.32 (95% CI, 1.27 to 1.37); 1.42 (95% CI, 1.35 to 1.50); 1.37 (95% CI, 1.25 to 1.50); and 1.32 (95% CI, 1.13 to 1.55). The increased ORs for eGFRs > 45 mL/min per 1.73 m(2) were sustained even after controlling for diabetes, heart failure, and hypertension. CONCLUSION This study demonstrated an increased risk of SA in patients with early CKD. Further evidence of a causal relationship should be sought in the hope that the detection and management of SA may improve the course of CKD.

Predictors of 30-Day Serious Events in Older Patients With Syncope

STUDY OBJECTIVE We identify predictors of 30-day serious events after syncope in older adults. METHODS We reviewed the medical records of older adults (age > or =60 years) who presented with syncope or near syncope to one of 3 emergency departments (EDs) between 2002 and 2005. Our primary outcome was occurrence of a predefined serious event within 30 days after ED evaluation. We used multivariable logistic regression to identify predictors of 30-day serious events. RESULTS Of 3,727 potentially eligible patients, 2,871 (77%) met all eligibility criteria. We excluded an additional 287 patients who received a diagnosis of a serious clinical condition while in the ED. In the final study cohort (n=2,584), we identified 173 (7%) patients who experienced a 30-day serious event. High-risk predictors included age greater than 90 years, male sex, history of an arrhythmia, triage systolic blood pressure greater than 160 mm Hg, abnormal ECG result, and abnormal troponin I level. A low-risk predictor was a complaint of near syncope rather than syncope. A risk score, generated by summing high-risk predictors and subtracting the low-risk predictor, can stratify patients into low- (event rate 2.5%; 95% confidence interval [CI] 1.4% to 3.6%), intermediate- (event rate 6.3%; 95% CI 5.1% to 7.5%), and high-risk (event rate 20%; 95% CI 15% to 25%) groups. CONCLUSION We identified predictors of 30-day serious events after syncope in adults aged 60 years and greater. A simple score was able to stratify these patients into distinct risk groups and, if externally validated, might have the potential to aid ED decisionmaking.

Automated Outreach to Increase Primary Adherence to Cholesterol-Lowering Medications

BACKGROUND Primary nonadherence occurs when new prescriptions are not dispensed. Little is known about how to reduce primary nonadherence. We performed a randomized controlled trial to evaluate an automated system to decrease primary nonadherence to statins for lowering cholesterol. METHODS Adult members of Kaiser Permanente Southern California with no history of statin use within the past year who did not fill a statin prescription after 1 to 2 weeks were passively enrolled. The intervention group received automated telephone calls followed 1 week later by letters for continued nonadherence; the control group received no outreach. The primary outcome was a statin dispensed up to 2 weeks after delivery of the letter. Secondary outcomes included refills at intervals up to 1 year. Intervention effectiveness was determined by intent-to-treat analysis and Fisher exact test. Subgroups were examined using logistic regression. RESULTS There were 2606 participants in the intervention group and 2610 in the control group. Statins were dispensed to 42.3% of intervention participants and 26.0% of control participants (absolute difference, 16.3%; P < .001). The relative risk for the intervention vs control group was 1.63 (95% CI, 1.50-1.76). Intervention effectiveness varied slightly by age (P = .045) but was effective across all age strata. Differences in the frequency of statin dispensations persisted up to 1 year (P < .001). CONCLUSIONS The intervention was effective in reducing primary nonadherence to statin medications. Because of low marginal costs for outreach, this strategy appears feasible for reducing primary nonadherence. This approach may generalize well to other medications and chronic conditions.

Racial Differences in Estimated GFR Decline, ESRD, and Mortality in an Integrated Health System

BACKGROUND Current evidence does not clearly identify the contribution of kidney function decline and mortality to racial disparities in end-stage renal disease (ESRD) incidence. We used observed estimated glomerular filtration rate (eGFR) to project the time of onset of kidney failure and examined mortality to better understand these racial disparities. STUDY DESIGN Retrospective cohort. SETTING & PARTICIPANTS Adult members of Kaiser Permanente Southern California in 2003-2009 with more than 2 serum creatinine tests and more than 180 days between tests: 526,498 whites, 350,919 Hispanics, 136,923 blacks, and 105,476 Asians. PREDICTOR Race/ethnicity. OUTCOMES ESRD (dialysis or transplantation); mortality. MEASUREMENTS eGFR decline was modeled using linear regression. Kidney failure was projected based on predicted eGFR <15 mL/min/1.73 m² at specified times. Racial differences in projected kidney failure and mortality in those with projected kidney failure were estimated with adjustment for age, sex, and entry eGFR. RESULTS Blacks had more extreme rates of eGFR decline (1st percentile, -23.6 mL/min/1.73 m² per year), followed by Hispanics (-20.9 mL/min/1.73 m² per year), whites (-20.1 mL/min/1.73 m² per year), and Asians (-17.6 mL/min/1.73 m² per year; P < 0.001). There were 25,065 whites, 11,368 Hispanics, 6,785 blacks, and 3,176 Asians with projected kidney failure during the study period. The ORs for projected kidney failure versus whites during CKD stages 3 and 4 were 1.54 (95% CI, 1.46-1.62) in blacks, 1.49 (95% CI, 1.42-1.56) in Hispanics, and 1.41 (95% CI, 1.32-1.51) in Asians. For those with projected kidney failure, the HRs of death versus whites during CKD stages 3 and 4 were 0.82 (95% CI, 0.77-0.88) in blacks, 0.67 (95% CI, 0.63-0.72) in Hispanics, and 0.58 (95% CI, 0.52-0.65) in Asians. LIMITATIONS Results may not generalize to the uninsured or subgroups within a race. Projected kidney failure was based on linear trends from clinically obtained eGFR. CONCLUSIONS We found more extreme rates of eGFR decline in blacks. Projected kidney failure during CKD stages 3 and 4 was high in blacks, Hispanics, and Asians relative to whites. Mortality for those with projected kidney failure was highest in whites. Differences in eGFR decline and mortality contributed to racial disparities in ESRD incidence.

Outcomes Associated with Race in Males with Nondialysis-Dependent Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Blacks are over-represented among dialysis patients, but they have better survival rates than whites. It is unclear if the over-representation of blacks on dialysis is due to faster loss of kidney function or greater survival (or both) in predialysis stages of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS We compared predialysis mortality, incidence of end stage renal disease (ESRD), and slopes of estimated GFR (eGFR) in 298 black versus 945 white male patients with moderate and advanced nondialysis-dependent CKD (NDD-CKD) from a single medical center. Mortality and ESRD incidence were compared in parametric survival models, and slopes of eGFR were assessed in mixed-effects models. RESULTS Blacks had lower crude mortality and higher crude ESRD incidence. The lower mortality in blacks was explained by differences in case mix, especially a lower prevalence of cardiovascular disease, and the higher incidence of ESRD was explained by differences in case mix and baseline kidney function. The slopes of eGFR were similar in blacks and whites. CONCLUSIONS Lower mortality in black versus white patients is also observed in NDD-CKD and can be accounted for by differences in clinical characteristics. Higher mortality of black patients in earlier stages of CKD may result in the selection of a subgroup with fewer comorbidities and better survival in later stages of CKD. The higher crude ESRD rate in blacks appears to result from lower mortality in late stages of CKD, not faster progression of CKD.

High-Deductible Health Insurance Plans: Efforts To Sharpen A Blunt Instrument

High deductible-based health insurance plans require consumers to pay for care until reaching the deductible amount. However, information is limited on how well consumers understand their benefits and how they respond to these costs. In telephone interviews, we found that consumers had limited knowledge about their deductibles yet frequently reported changing their care-seeking behavior because of the cost. Poor knowledge limited the effects of the deductible design, with some consumers avoiding care for services that were exempt from the deductible. Consumers need more information and decision support to understand their benefits and to differentiate when care is necessary, discretionary, or unnecessary.

Association of Serum Lipids and Coronary Heart Disease in Contemporary Observational Studies

Background— The use of statins increased among US adults with high coronary heart disease (CHD) risk after publication of the 2001 cholesterol treatment guidelines. Methods and Results— We analyzed the association between lipids and CHD among 9578 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants and 346 595 Kaiser Permanente Southern California (KPSC) members with baseline lipid measurements in 2003 to 2007. We performed the same analyses among 14 590 Atherosclerosis Risk In Communities (ARIC) study participants with lipid measurements in 1987 to 1989. Analyses were restricted to blacks and whites 45 to 64 years of age without CHD who were not taking statins at baseline. Total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured at baseline. Low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, and ratios of total to high-density lipoprotein cholesterol and triglycerides to high-density lipoprotein cholesterol were calculated. The prevalence of diabetes mellitus, history of stroke, and antihypertensive medication use increased at higher low-density lipoprotein cholesterol in ARIC but not in REGARDS or KPSC. Over 8.9 years of follow-up, 225 CHD events occurred in REGARDS, 6547 events in KPSC, and 583 events in ARIC. After multivariable adjustment, less favorable lipid levels were associated with higher hazard ratios for CHD in ARIC. These associations were attenuated in REGARDS and KPSC. For example, the hazard ratio associated with the highest versus lowest quartile of low-density lipoprotein cholesterol (≥146 versus ⩽102 mg/dL) was 1.89 (95% confidence interval, 1.42–2.51) in ARIC, 1.25 (95% confidence interval, 0.81–1.92) in REGARDS, and 1.49 (95% confidence interval, 1.38–1.61) in KPSC. Conclusion— The association between lipids and CHD in contemporary studies may be attenuated by the preferential use of statins by high-risk individuals.

Race and Ethnicity Data Quality and Imputation Using U.S. Census Data in an Integrated Health System: The Kaiser Permanente Southern California Experience

Research on racial and ethnic disparities using health system databases can shed light on the usual health care and outcomes of large numbers of individuals so that health inequities can be better understood and addressed. Such research often suffers from limitations in race/ethnicity data quality. We examined the quality of race/ethnicity data in a large, diverse, integrated health system that repeatedly collects these data on utilization of services. We tested the accuracy of Bayesian Improved Surname Geocoding for imputation of race/ethnicity data. Administrative race/ethnicity data were accurate as judged by comparison with self-report in adults. The Bayesian Improved Surname Geocoding method produced imputation results far better than chance assignment for the four most common race/ethnicity groups in the health system: Whites, Hispanics, Blacks, and Asians. These results support renewed efforts to conduct studies of racial and ethnic disparities in large health systems.

Health plan administrative records versus birth certificate records: quality of race and ethnicity information in children

BackgroundTo understand racial and ethnic disparities in health care utilization and their potential underlying causes, valid information on race and ethnicity is necessary. However, the validity of pediatric race and ethnicity information in administrative records from large integrated health care systems using electronic medical records is largely unknown.MethodsInformation on race and ethnicity of 325,810 children born between 1998-2008 was extracted from health plan administrative records and compared to birth certificate records. Positive predictive values (PPV) were calculated for correct classification of race and ethnicity in administrative records compared to birth certificate records.ResultsMisclassification of ethnicity and race in administrative records occurred in 23.1% and 33.6% children, respectively; the majority due to missing ethnicity (48.3%) and race (40.9%) information. Misclassification was most common in children of minority groups. PPV for White, Black, Asian/Pacific Islander, American Indian/Alaskan Native, multiple and other was 89.3%, 86.6%, 73.8%, 18.2%, 51.8% and 1.2%, respectively. PPV for Hispanic ethnicity was 95.6%. Racial and ethnic information improved with increasing number of medical visits. Subgroup analyses comparing racial classification between non-Hispanics and Hispanics showed White, Black and Asian race was more accurate among non-Hispanics than Hispanics.ConclusionsIn children, race and ethnicity information from administrative records has significant limitations in accurately identifying small minority groups. These results suggest that the quality of racial information obtained from administrative records may benefit from additional supplementation by birth certificate data.