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HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood.Integrated health care system.We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex.The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively).Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH.

Limited data exist in large, representative populations about whether the risk of thromboembolic events varies after receiving four-factor human prothrombin complex concentrate (4F-PCC) versus treatment with human plasma for urgent reversal of oral vitamin K antagonist therapy. We conducted a multicenter observational study to compare the 45-day risk of thromboembolic events in adults with warfarin-associated major bleeding after treatment with 4F-PCC (Kcentra®) or plasma. Hospitalized patients in two large integrated healthcare delivery systems who received 4F-PCC or plasma for reversal of warfarin due to major bleeding from January 1, 2008 to March 31, 2020 were identified and were matched 1:1 on potential confounders and a high-dimensional propensity score. Arterial and venous thromboembolic events were identified up to 45 days after receiving 4F-PCC or plasma from electronic health records and adjudicated by physician review. Among 1119 patients receiving 4F-PCC and a matched historical cohort of 1119 patients receiving plasma without a recent history of thromboembolism, mean (SD) age was 76.7 (10.5) years, 45.6% were women, and 9.4% Black, 14.6% Asian/Pacific Islander, and 15.7% Hispanic. The 45-day risk of thromboembolic events was 3.4% in those receiving 4F-PCC and 4.1% in those receiving plasma (P = 0.26; adjusted hazard ratio 0.76; 95% confidence interval 0.49-1.16). The adjusted risk of all-cause death at 45 days post-treatment was lower in those receiving 4F-PCC compared with plasma. Among a large, ethnically diverse cohort of adults treated for reversal of warfarin-associated bleeding, receipt of 4F-PCC was not associated with an excess risk of thromboembolic events at 45 days compared with plasma therapy.

The impact of the novel coronavirus disease 2019 (COVID-19) pandemic on diet and nutrition among older adults with chronic medical conditions have not been well-described.We conducted a survey addressing (1) food access, (2) diet quality and composition, (3) nutritional understanding, and (4) attitudes towards research among adults with heart failure (HF) within an integrated health system. Adults (≥18 years) with diagnosed HF and at least one prior hospitalization for HF within the last 12 months were approached to complete the survey electronically or by mail. Outcomes included all-cause and HF-specific hospitalizations and all-cause death was ascertained via the electronic health record.Among 1212 survey respondents (32.5% of eligible patients) between May 18, 2020 and September 30, 2020, mean ± SD age was 77.9 ± 11.4 years, 50.1% were women, and median (25th-75th) left ventricular ejection fraction was 55% (40%-60%). Overall, 15.1% of respondents were food insecure, and only 65% of participants answered correctly more than half of the items assessing nutritional knowledge. Although most respondents were willing to participate in future research, that number largely declined for studies requiring blood draws (32.2%), study medication (14.4%), and/or behavior change (27.1%). Food security, diet quality, and nutritional knowledge were not independently associated with outcomes at 90 or 180 days.In a cohort of older adults with HF and multiple comorbidities, a significant proportion reported issues with food access, diet quality, and nutritional knowledge during the COVID-19 pandemic. Future research should evaluate interventions targeting these domains in at-risk individuals.

Aims Human immunodeficiency virus (HIV) increases the risk of heart failure (HF), but whether it influences subsequent morbidity and mortality remains unclear. Methods and results We investigated the risks of hospitalization for HF, HF-related emergency department (ED) visits, and all-cause death in an observational cohort of incident HF patients with and without HIV using data from three large US integrated healthcare delivery systems. We estimated incidence rates and adjusted hazard ratios (aHRs) by HIV status at the time of HF diagnosis for subsequent outcomes. We identified 448 persons living with HIV (PLWH) and 3429 without HIV who developed HF from a frequency-matched source cohort of 38 868 PLWH and 386 586 without HIV. Mean age was 59.5 ± 11.3 years with 9.8% women and 31.8% Black, 13.1% Hispanic, and 2.2% Asian/Pacific Islander. Compared with persons without HIV, PLWH had similar adjusted rates of HF hospitalization [aHR 1.01, 95% confidence interval (CI): 0.81–1.26] and of HF-related ED visits [aHR 1.22 (95% CI: 0.99–1.50)], but higher adjusted rates of all-cause death [aHR 1.31 (95% CI: 1.08–1.58)]. Adjusted rates of HF-related morbidity and all-cause death were directionally consistent across a wide range of CD4 counts but most pronounced in the subset with a baseline CD4 count Conclusion In a large, diverse cohort of adults with incident HF receiving care within integrated healthcare delivery systems, PLWH were at an independently higher risk of all-cause death but not HF hospitalizations or HF-related ED visits. Future studies investigating modifiable HIV-specific risk factors may facilitate more personalized care to optimize outcomes for PLWH and HF.

BackgroundVariation in outcomes by race/ethnicity in adults with heart failure (HF) has been previously observed. Identifying factors contributing to these variations could help target interventions. We evaluated the association of race/ethnicity with HF outcomes and potentially contributing factors within a contemporary HF cohort.Methods and ResultsWe identified members of Kaiser Permanente Northern California, a large integrated healthcare delivery system, who were diagnosed with HF between 2012 and 2016 and had at least 1 year of prior continuous membership and left ventricular ejection fraction data. We used Cox regression with time‐dependent covariates to evaluate the association of self‐identified race/ethnicity with HF or all‐cause hospitalization and all‐cause death, with backward selection for potential explanatory variables. Among 34 621 patients with HF, compared with White patients, Black patients had a higher rate of HF hospitalization (adjusted hazard ratio [HR], 1.28; 95% CI, 1.18–1.38) but a lower rate of death (adjusted HR, 0.78; 95% CI, 0.72–0.85). In contrast, Asian/Pacific Islander patients had similar rates of HF hospitalization, but lower rates of all‐cause hospitalization (adjusted HR, 0.89; 95% CI, 0.85–0.93) and death (adjusted HR, 0.75; 95% CI, 0.69–0.80). Hispanic patients also had a lower rate of death (adjusted HR, 0.85; 95% CI, 0.80–0.91). Sensitivity analyses showed that effect sizes for Black patients were larger among patients with reduced ejection fraction.ConclusionsIn a contemporary and diverse population with HF, Black patients experienced a higher rate of HF hospitalization and a lower rate of death compared with White patients. In contrast, selected outcomes for Asian/Pacific Islander and Hispanic patients were more favorable compared with White patients. The observed differences were not explained by measured potentially modifiable factors, including pharmacological treatment. Future research is needed to identify explanatory mechanisms underlying ongoing racial/ethnic variation to target potential interventions.

Background: In-person clinic follow-up within 7 days after discharge from a heart failure hospitalization is associated with lower 30-day readmission. However, health systems and patients may find it difficult to complete an early postdischarge clinic visit, especially during the current pandemic. We evaluated the effect on 30-day readmission and death of follow-up within 7 days postdischarge guided by an initial structured nonphysician telephone visit compared with follow-up guided by an initial clinic visit with a physician. Methods and Results: We conducted a pragmatic randomized trial in a large integrated healthcare delivery system. Adults being discharged home after hospitalization for heart failure were randomly assigned to either an initial telephone visit with a nurse or pharmacist to guide follow-up or an initial in-person clinic appointment with primary care physicians providing usual care within the first 7 days postdischarge. Telephone appointments included a structured protocol enabling medication titration, laboratory ordering, and booking urgent clinic visits as needed under physician supervision. Outcomes included 30-day readmissions and death and frequency and type of completed follow-up within 7 days of discharge. Among 2091 participants (mean age 78 years, 44% women), there were no significant differences in 30-day heart failure readmission (8.6% telephone, 10.6% clinic, P =0.11), all-cause readmission (18.8% telephone, 20.6% clinic, P =0.30), and all-cause death (4.0% telephone, 4.6% clinic, P =0.49). Completed 7-day follow-up was higher in 1027 patients randomized to telephone follow-up (92%) compared with 1064 patients assigned to physician clinic follow-up (79%, P P Conclusions: Early, structured telephone follow-up after hospitalization for heart failure can increase 7-day follow-up and reduce in-person visits with comparable 30-day clinical outcomes within an integrated care delivery framework. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03524534.

RESEARCH OBJECTIVE: Heart failure (HF)–related hospitalizations are a growing public health burden, especially among older adults. Risk calculators for HF readmissions identify patients at high risk for readmissions who may benefit from outpatient interventions to improve outcomes and prevent readmissions. We hypothesized that incorporating additional variables and using machine learning approaches would improve the performance of these existing 30‐day readmission risk calculators. STUDY DESIGN: We evaluated the performance of several published risk calculators for predicting 30‐day readmission after heart failure hospitalizations: 1) using updating the coefficients based on data from a new, ethnically diverse HF population; 2) developing a new model that incorporates additional variables in addition to updated coefficients; and 3) developing new models with all variables using machine learning approaches. We used an 80%/20% split sampling for development and validation testing. The risk calculators tested included the LACE+ Index and Yale CORE, which included traditional clinical variables such as comorbidities, laboratory values, prior utilization, and vital signs. For the model with additional variables, we included all variables used in the original models with the addition of Comorbidity Point Score (COPS), Laboratory‐based Acute Physiology Score (LAPS), cardiovascular medications, discharge status, and socioeconomic status. We evaluated the original model and the original plus model, the additional variables using logistic regression. For the machine learning approaches, we used lasso penalized regression and gradient boosting with k‐fold cross‐validation to avoid overfitting. We assessed model performance using area under the curve (AUC) and calibration plots. POPULATION STUDIED: We identified 38,234 adults hospitalized for HF between 2012 and 2017 within Kaiser Permanente Northern California, an integrated health care delivery system covering over 4.4 million members. PRINCIPAL FINDINGS: Discrimination (AUC) was poor using original models, LACE+ [0.60 (0.59‐0.62)] and Yale CORE [0.57 (0.56‐0.59)]. Including the additional variables resulted in a small improvement in AUC: LACE+ [0.62 (0.60‐0.64)] and Yale CORE [0.62 (0.60‐0.64)]. The lasso model [0.67 (0.65, 0.68) and gradient boosting model [0.67 (0.65‐0.68)] resulted in greater improvement. Calibration plots showed generally good calibration across all models with modest improvements after adding the additional data domains and using the machine learning approaches. CONCLUSIONS: Incorporating additional data domains led to small, statistically significant improvements in model discrimination while maintaining good calibration for published models to predict readmission. Machine learning approaches resulted in even greater improvement and overall moderate discrimination. IMPLICATIONS FOR POLICY OR PRACTICE: We were able to increase the utility of these published risk calculators for readmission after discharge from a HF hospitalization by including additional data domains and using machine learning approaches. Health systems attempting to adapt published risk calculators for readmissions should consider including these data domains and using machine learning approaches to improve performance. PRIMARY FUNDING SOURCE: The Permanente Medical Group Delivery Science Research Program.

Acute Myocardial Infarction and Covid-19 Data from the Kaiser Permanente Northern California health care system were used to compare rates of hospitalization for acute MI from March 4 through April...

Background The survival benefit associated with cumulative adherence to multiple clinical and lifestyle‐related guideline recommendations for secondary prevention after acute myocardial infarction ( AMI ) is not well established. Methods and Results We examined adults with AMI (mean age 68 years; 64% men) surviving at least 30 (N=25 778) or 90 (N=24 200) days after discharge in a large integrated healthcare system in Northern California from 2008 to 2014. The association between all‐cause death and adherence to 6 or 7 secondary prevention guideline recommendations including medical treatment (prescriptions for β‐blockers, renin‐angiotensin‐aldosterone system inhibitors, lipid medications, and antiplatelet medications), risk factor control (blood pressure AMI was evaluated with Cox proportional hazard models. To allow patients time to achieve low‐density lipoprotein cholesterol AMI . Overall guideline adherence was high (35% and 34% met 5 or 6 guidelines at 30 days; and 31% and 23% met 6 or 7 at 90 days, respectively). Greater guideline adherence was independently associated with lower mortality ( hazard ratio, 0.57 [95% CI, 0.49–0.66] for those meeting 7 and hazard ratio, 0.69 [95% CI, 0.61–0.78] for those meeting 6 guidelines versus 0 to 3 guidelines in 90‐day models, with similar results in the 30‐day models), with significantly lower mortality per each additional guideline recommendation achieved. Conclusions In a large community‐based population, cumulative adherence to guideline‐recommended medical therapy, risk factor control, and lifestyle changes after AMI was associated with improved long‐term survival. Full adherence was associated with the greatest survival benefit.

Introduction: Heart failure (HF)-related hospitalizations are a growing public health burden. We evaluated two published risk calculators for predicting 30-day readmission after HF hospitalizations: 1) using the original coefficients, 2) updating the coefficients 3) developing a new model with additional variables and updated coefficients. Hypothesis: Recalibrating model coefficients and adding variables would improve the performance of existing 30-day readmission risk calculators. Methods: We identified 45,059 adults hospitalized for HF between 2012-2017 within Kaiser Permanente Northern California, an integrated healthcare delivery system. We used split sampling for development and validation testing. The risk calculators tested included: LACE+ Index and Yale CORE. We used logistic regression on our population to derive the recalibrated coefficients. For the model with additional variables, we included all variables used in the original models plus additional variables, including cardiovascular medication use and socioeconomic status. We used gradient boosting with k-fold cross validation to avoid overfitting. We assessed model performance using area under the curve (AUC) and calibration plots. Results: Discrimination (AUC) was poor using original models: LACE+ [0.56 (0.54-0.58)] and Yale CORE [0.55 (0.54-0.57)]. Recalibrating coefficients resulted in small improvements for LACE+ [0.58 (0.57, 0.60)] and Yale CORE [0.58 (0.57, 0.60)]. Adding variables resulted in a modest improvement for the gradient boosting model [0.61 (0.59, 0.62)]. Calibration plots (Figure 1) showed good calibration except for the Yale CORE model with the original coefficients. Conclusions: Recalibrating coefficients and incorporating prior medication and socioeconomic status led to modest, significant improvements in discrimination while maintaining good calibration. However, overall performance improvements are needed to increase the utility of these published risk calculators to predict readmission.

Patients with heart failure (HF) and preserved (HFpEF) or borderline preserved ejection fraction (HFbEF) outnumber patients with HF and reduced ejection fraction (HFrEF), but limited data exist on outcomes in community-based populations of these patients. We examined clinical outcomes in a diverse population of adults with HFrEF, HFbEF, and HFpEF. All adults with diagnosed HF from 2005 to 2012 in Kaiser Permanente Northern California were categorized by left ventricular systolic function as HFpEF (EF ≥50%), HFbEF (EF 41-49%), or HFrEF (EF ≤40%). Demographics, clinical characteristics, and therapies were obtained from electronic records. Outcomes included death, HF hospitalization, and HF-related emergency department (ED) visit. In 28,914 eligible HF patients, there were 52% HFpEF, 16% HFbEF, and 32% HFrEF, with mean age 72.8 years and 45% women. During median follow-up of 3.5 years, crude rates (per 100 person-years) of death, HF hospitalization, and HF-related ED visit were 14.5 (95% CI 14.3 to 14.7), 15.8 (15.5 to 16.0), and 38.2 (37.8 to 38.5), respectively. Compared with HFrEF patients, adjusted hazard ratios of death, HF hospitalization, and HF-related ED visit for HFpEF patients were 0.82 (0.79 to 0.85), 0.72 (0.68 to 0.75), and 0.94 (0.90 to 0.99), respectively, and for HFbEF patients were 0.84 (0.79 to 0.88), 0.79 (0.73 to 0.84), and 0.90 (0.84 to 0.96), respectively. In conclusion, within a large community-based HF cohort, adjusted rates of death, HF hospitalization, and HF-related ED visits were similar in HFpEF and HFbEF patients, but higher in HFrEF patients. Regardless of systolic function, however, long-term mortality and morbidity in all HF patients remain high, reinforcing the need for novel strategies to improve long-term outcomes.

Background Beckman Coulter recently released a new cardiac troponin I (cTnI) assay, AccuTnI+3, for the Access 2 and DxI platforms. We validated the stated 99th percentile (20 ng/l) using a large population of healthy adults representative of the Northern California population. Methods Within a large sample of healthy adult members receiving care at Kaiser Permanente, cTnI was quantified in residual specimens using the AccuTnI + 3 assay. Patients were selected based on pre-defined criteria extracted from a comprehensive electronic medical record. All specimens with a cTnI concentration > 30 ng/l were repeated; specimens that had a reproducible result > 30 ng/l were subject to heterophile blocking procedure. 99th percentiles were calculated based on age, sex, race and body mass index categories. Results Among 1764 tested subjects, the 99th percentile for all samples was 25 ng/l. Sex differences were observed; the male and female 99th percentiles were 31 and 21 ng/l, respectively (p = 0.001). Age (range evaluated 18–89 y, median 47 y) also had a significant influence on the value (p = 0.003), but there were no significant differences by race. False positive results were detected in 0.9% of specimens (0.6% “fliers” and 0.3% heterophile antibodies), corresponding to 52% of all results > 30 ng/l. Conclusions Among a large, representative cohort of healthy adults, we found a 99th percentile value consistent with prior studies based on highly selected small patient samples. Sex and age-specific upper reference limits for cTnI should be considered. In this cohort, about half the findings above the 99th percentile were false positives. Avoiding reporting erroneous results requires implementation of quality indicators.

Renal recovery after dialysis-requiring acute kidney injury (AKI-D) is an important clinical and patient-centered outcome. Here we examined whether the pre-admission proteinuria level independently influences risk for non-recovery after AKI-D in a community-based population. All adult members of Kaiser Permanente Northern California who experienced AKI-D between January 1, 2009 and September 30, 2015 were included. Pre-admission proteinuria levels were determined by dipstick up to four years before the AKI-D hospitalization and the outcome was renal recovery (survival and dialysis-independence four weeks and more) at 90 days after initiation of renal replacement therapy. We used multivariable logistic regression to adjust for baseline estimated glomerular filtration rate (eGFR), age, sex, ethnicity, short-term predicted risk of death, comorbidities, and medication use. Among 5,347 adults with AKI-D, the mean age was 66 years, 59% were men, and 50% were white. Compared with negative/trace proteinuria, the adjusted odds ratios for non-recovery (continued dialysis-dependence or death) were 1.47 (95% confidence interval 1.19–1.82) for 1+ proteinuria and 1.92 (1.54–2.38) for 2+ or more proteinuria. Among survivors, the crude probability of recovery ranged from 83% for negative/trace proteinuria with baseline eGFR over 60 mL/min/1.73m 2 to 25% for 2+ or more proteinuria with eGFR 15–29 mL/min/1.73m 2 . Thus, the pre-AKI-D level of proteinuria is a graded, independent risk factor for non-recovery and helps to improve short-term risk stratification for patients with AKI-D.

Background Acute kidney injury (AKI) is a known complication after coronary revascularization, but few studies have directly compared the incidence of AKI after coronary artery bypass surgery (CABG) or after percutaneous coronary intervention (PCI) in similar patients. Objectives The aim of this study was to investigate whether multivessel CABG compared with PCI as an initial revascularization strategy is associated with a higher risk for AKI. Methods A retrospective analysis of patients undergoing first documented coronary revascularization was conducted using 2 complementary cohorts: 1) Kaiser Permanente Northern California, a diverse, integrated health care delivery system; and 2) Medicare beneficiaries, a large, nationally representative older cohort. AKI was defined in the Kaiser Permanente Northern California cohort by an increase in serum creatinine of ≥0.3 mg/dl or ≥150% above baseline and in the Medicare cohort by discharge diagnosis codes and the use of dialysis. Results The incidence of AKI was 20.4% in the Kaiser Permanente Northern California cohort and 6.2% in the Medicare cohort. The incidence of AKI requiring dialysis was Conclusions AKI is common after multivessel coronary revascularization and is more likely after CABG than after PCI. The risk for AKI should be considered when choosing a coronary revascularization strategy, and ways to prevent AKI after coronary revascularization are needed.

Recent studies that have assessed the comparative effectiveness between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with end-stage renal disease (ESRD) that have included analyses of temporal trends in mortality have noted mixed results.We conducted an observational longitudinal cohort study of all adults with ESRD undergoing CABG or PCI within Kaiser Permanente Northern California. The primary predictor, index period of revascularization, was categorized into 3 periods: 1996-1999 (reference), 2000-2003, and 2004-2008, with the primary outcome being 3-year all-cause mortality. A multivariable Cox regression model with the assumption of independent censoring was used to determine the adjusted relative risk of the primary predictor.Among 1015 ESRD patients, 3-year mortality showed no significant change in the 2000-2003 period but was lower during the 2004-2008 period with an adjusted hazard ratio of 0.66 (95% confidence interval: 0.49-0.88; trend test p = 0.01). No change in 30-day mortality was noted. Further adjustment for receipt of medications at baseline and after revascularization did not materially affect risk estimates. No significant interactions were observed between the type of revascularization (CABG or PCI) and the period of the index revascularization.Among a high-risk cohort of patients with ESRD and coronary artery disease within Kaiser Permanente Northern California who were referred for coronary revascularization by either CABG or PCI, the relative risk of mortality in the 2004-2008 period decreased by 34% compared with the 1996-1999 period, with the benefit primarily in the decrease in late mortality.

Background: In-person clinic follow-up within 7 days after discharge from a heart failure hospitalization is associated with lower 30-day readmission. However, health systems and patients may find ...

Risk calculators for short-term outcomes after percutaneous coronary intervention (PCI) exist, but less is known about predictors of long-term outcomes and resource utilization. We retrospectively studied adults >20 yrs old receiving PCI from 2008-2012 in Kaiser Permanente Northern California, a

ObjectivesThis study sought to compare use of evidence-based secondary preventive medications after coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI).BackgroundUse of cardioprotective medication after coronary revascularization has been inconsistent and relatively low in older studies.MethodsWe studied patients in a large integrated healthcare delivery system who underwent CABG or PCI for new onset coronary disease. We used data from health plan databases about prescriptions dispensed during the first year after initial coronary revascularization to identify patients who never filled a prescription and to calculate the medication possession ratio among patients who filled at least 1 prescription. We focused on angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), beta-blockers, and statins.ResultsBetween 2000 and 2007, 8,837 patients with new onset coronary disease underwent initial CABG, and 14,516 underwent initial PCI. Patients receiving CABG were more likely than patients receiving PCI to not fill a prescription for a statin (7.1% vs. 4.8%, p < 0.0001) or for an ACEI/ARB (29.1% vs. 22.4%, p < 0.0001), but similar proportions never filled a prescription for a beta-blocker (6.4% vs. 6.1%). Among those who filled at least 1 prescription post-revascularization, patients receiving CABG had lower medication possession ratios than patients receiving PCI for ACEI/ARBs (69.4% vs. 77.8%, p < 0.0001), beta-blockers (76.1% vs. 80.6%, p < 0.0001), and statins (82.7% vs. 84.2%, p < 0.001).ConclusionsPatients who received CABG were generally less likely than patients who received PCI to fill prescriptions for secondary preventive medications and to use those medications consistently in the first year after the procedure.

Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations.We examined trends in hospitalized acute myocardial infarction incidence among adults aged ≥25 years in 13 US health plans in the Cardiovascular Research Network. The first hospitalization per member for acute myocardial infarction overall and for ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge codes in each calendar year from 2000 through 2008. Age- and sex-adjusted incidence was calculated per 100,000 person-years using direct adjustment with 2000 US census data.Between 2000 and 2008, we identified 125,435 acute myocardial infarction hospitalizations. Age- and sex-adjusted incidence rates (per 100,000 person-years) of acute myocardial infarction decreased an average 3.8%/y from 230.5 in 2000 to 168.6 in 2008. Incidence of ST-segment elevation myocardial infarction decreased 8.7%/y from 104.3 in 2000 to 51.7 in 2008, whereas incidence of non-ST-segment elevation myocardial infarction increased from 126.1 to 129.4 between 2000 and 2004 and then decreased thereafter to 116.8 in 2008. Age- and sex-specific incidence rates generally reflected similar patterns, with relatively larger decreases in ST-segment elevation myocardial infarction rates in women compared with men. As compared with 2000, the age-adjusted incidence of ST-segment elevation myocardial infarction in 2008 was 48% lower among men and 61% lower among women.Among a large, diverse, multicenter community-based insured population, there were significant decreases in incidence of hospitalized acute myocardial infarction and the more serious ST-segment elevation myocardial infarctions between 2000 and 2008. Decreases in ST-segment elevation myocardial infarctions were most pronounced among women. While ecologic in nature, these secular decreases likely reflect, at least in part, results of improvement in primary prevention efforts.

Background The presence of multimorbidity is known to be related to adverse clinical outcomes. However, its association with mortality in patients undergoing cardiac valve replacement is not known. Methods Multimorbidity (as a continuous variable) was characterized in adults receiving cardiac valve replacement surgery between 2008 and 2012 within Kaiser Permanente Northern California based on information from health plan electronic health records. Our primary outcome was 3-year all-cause mortality after surgery. We used Cox proportional hazards regression to evaluate the independent association of each additional comorbidity with mortality. Results Among 3686 eligible patients, mean age was 67.9±13.5years and median comorbidity burden was 3 (IQR: 2). The presence of most individual comorbidities except hypertension and hyperlipidemia did not occur in isolation. The unadjusted annual incidence (per 100 person-years) of death increased with higher comorbidity burden: ≤1: 4.61 (95% CI: 3.29–6.45), 2–3: 13.7 (95% CI: 11.9–15.8), 4–5: 23.6 (95% CI: 20.6–26.9), and ≥6: 43.4(95% CI: 34.6–54.4). Advancing age, diabetes mellitus, cerebrovascular accident, heart failure, lung disease, urgent status and use of aldosterone-receptor antagonists were independently associated with an increased risk of mortality. In multivariable analyses, each additional comorbidity was significantly associated with an increased risk of long-term (adjusted hazard ratio (HR) 1.30, 95% CI: 1.22–1.39) but not short-term mortality (HR 0.92, 95% CI: 0.80–1.07). Conclusions Our study demonstrated that multimorbidity in patients undergoing cardiac valve replacement is significantly associated with long-term but not short-term mortality.

Background: The clinical effects of age occur over an age continuum, yet age as a primary predictor is often analyzed using arbitrary age cut-points. Objective: To assess whether transformation of a continuous variable such as age using a spline function can uncover nonlinear associations between age and cardiovascular outcomes. Design: Observational retrospective cohort study in 1015 Kaiser Permanente Northern California patients with end-stage renal disease after index coronary revascularization. Age, the primary predictor, was modeled by 5 different techniques: 1) dichotomized at 65 years or older; 2) at 80 years or older (as a sensitivity analysis); 3) categorized as younger than 55 years (reference), 55 to 64, 65 to 74, and 75 years or older; 4) linear (every 5 years) variable; and 5) nonlinear by transformation into a cubic spline. Age categories were changed in a sensitivity analysis. Main Outcome Measures: Primary and secondary outcomes were all-cause mortality and repeat revascularization, respectively. Results: Graphical assessment demonstrated that age dichotomized at either 65 years and older or 80 years and older led to loss of information. Categorized age underestimated or overestimated risk at the extremes of age. A sensitivity analysis demonstrated that an arbitrary change in the age category led to a different conclusion. Age modeled linearly adequately represented mortality risk but was suboptimal with repeat revascularization. Only the cubic spline demonstrated the nonlinear association between age and repeat revascularization. Conclusion: Employing the continuous variable age as a case study, we have demonstrated that the use of flexible transformations, such as spline functions, can unearth clinically meaningful associations that would not have been possible otherwise. Future research should determine whether incorporation of these methods can improve decision making at a population level.

Younger women use both internal medicine and obstetrics-gynecology (OBGYN) clinics as primary sources of health care. However, the role of OBGYN clinics in cardiovascular disease prevention is largely unexplored. The objective of this study was to examine rates of hypertension recognition in women

The epidemiology of heart failure (HF) has shifted, as incident cases of HF with Preserved (HFpEF) and Borderline Ejection Fraction (HFbEF) now outnumber cases of HF with Reduced Ejection Fraction (HFrEF). However, limited data exist on outcomes by HF type, especially HFbEF, within contemporary

Recent substantial reductions in acute myocardial infarction (AMI) rates have been reported in various patient populations [(1)][1]. Within the same health care delivery system, we extended an earlier analysis from 1999 to 2008 to examine whether these reductions have persisted into the most recent

Background: Age is a known risk factor for mortality after cardiac valve replacement. Little is known of the interaction between age and end stage renal disease (ESRD). To better comprehend the relationship between age as a continuum and cardiovascular outcomes, assessment of nonlinear relationships needs to be undertaken. Methods: We enrolled 3,792 patients (3.1% ESRD) who underwent a cardiac valve surgery between January 1, 2000 and December 31, 2012 in Kaiser Permanente Northern California. Age was modeled as a linear variable (every 5 years) and as a cubic spline. The primary outcome was all-cause mortality at 5-years. We subsequently fit unadjusted logistic models and graphed the model-predicted probability of mortality versus age by the 2 aforementioned methods. Results: ESRD patients were slightly younger, had higher baseline comorbidities, prior cardiovascular interventions, and urgent surgeries. The odds of death with advancing age was greatly attenuated in the ESRD cohort (1.05, 95% CI: 0.90-1.23) compared to the non-ESRD cohort (1.32, 95% CI: 1.26-1.38). We noted that age had an effect modification on ESRD (p interaction=0.03). Furthermore, only in the ESRD cohort, age was noted to have a non-linear relationship with mortality with a peak risk around 60 years of age and a subsequent decrease (Figure 1). Conclusions: ESRD continues to be a high-risk cohort for mortality after cardiac valve replacement with advancing age having a lesser role in ESRD patients. Assessment of the continuum of age by non-linear methods is crucial to improving our care for the elderly.

Background Inadequate recruitment of women and an exclusion of patients with end-stage renal disease (ESRD) in coronary revascularization trials have led to knowledge gaps of gender-based outcomes. Hypothesis Women have equivalent cardiovascular outcomes when compared to men. Methods We conducted a retrospective observational study utilizing Kaiser Permanente Northern California (KPNC) databases and identified 1015 adults with ESRD who underwent coronary revascularization between 1996 and 2008. We ascertained baseline characteristics, primary (mortality at 5 years) and secondary (myocardial infarction [MI] and repeat revascularization) outcomes from KPNC databases, state death certificates, and Social Security Administration files. A multivariable logistic regression was used to determine the association of gender to the prespecified outcomes. Results Men and women were similar in age (P = 0.23). The mean number of baseline comorbidities was higher in women (2.7, 95% confidence interval [CI]: 2.5-2.9) compared to men (2.3, 95% CI: 2.1-2.4, P = 0.0002). The risk-adjusted odds ratios (OR) of female gender to death at 5 years (OR: 1.12, 95% CI: 0.83-1.52), MI (OR: 1.19, 95% CI: 0.86-1.64), and repeat revascularization (OR: 1.01, 95% CI: 0.70-1.45) were similar to men. Age modified the effect of gender for the primary outcome death (Pinteraction

BACKGROUND: Inadequate recruitment of women and an exclusion of patients with end‐stage renal disease (ESRD) in coronary revascularization trials have led to knowledge gaps of gender‐based outcomes. HYPOTHESIS: Women have equivalent cardiovascular outcomes when compared to men. METHODS: We conducted a retrospective observational study utilizing Kaiser Permanente Northern California (KPNC) databases and identified 1015 adults with ESRD who underwent coronary revascularization between 1996 and 2008. We ascertained baseline characteristics, primary (mortality at 5 years) and secondary (myocardial infarction [MI] and repeat revascularization) outcomes from KPNC databases, state death certificates, and Social Security Administration files. A multivariable logistic regression was used to determine the association of gender to the prespecified outcomes. RESULTS: Men and women were similar in age (P = 0.23). The mean number of baseline comorbidities was higher in women (2.7, 95% confidence interval [CI]: 2.5‐2.9) compared to men (2.3, 95% CI: 2.1‐2.4, P = 0.0002). The risk‐adjusted odds ratios (OR) of female gender to death at 5 years (OR: 1.12, 95% CI: 0.83‐1.52), MI (OR: 1.19, 95% CI: 0.86‐1.64), and repeat revascularization (OR: 1.01, 95% CI: 0.70‐1.45) were similar to men. Age modified the effect of gender for the primary outcome death (P (interaction)

Acute kidney injury (AKI) is a known complication after coronary revascularization, but few studies have directly compared the incidence of AKI after coronary artery bypass surgery (CABG) or after percutaneous coronary intervention (PCI) in similar patients.The aim of this study was to investigate whether multivessel CABG compared with PCI as an initial revascularization strategy is associated with a higher risk for AKI.A retrospective analysis of patients undergoing first documented coronary revascularization was conducted using 2 complementary cohorts: 1) Kaiser Permanente Northern California, a diverse, integrated health care delivery system; and 2) Medicare beneficiaries, a large, nationally representative older cohort. AKI was defined in the Kaiser Permanente Northern California cohort by an increase in serum creatinine of ≥0.3 mg/dl or ≥150% above baseline and in the Medicare cohort by discharge diagnosis codes and the use of dialysis.The incidence of AKI was 20.4% in the Kaiser Permanente Northern California cohort and 6.2% in the Medicare cohort. The incidence of AKI requiring dialysis was1%. CABG was associated with a 2- to 3-fold significantly higher adjusted odds for developing AKI compared with PCI in both cohorts.AKI is common after multivessel coronary revascularization and is more likely after CABG than after PCI. The risk for AKI should be considered when choosing a coronary revascularization strategy, and ways to prevent AKI after coronary revascularization are needed.

Background: Prior cardiovascular studies have often dichotomized the continuous variable age at a certain pre-specified cutoff which is thought to lead to a loss of information. Methods: To further understand this loss of information we conducted a retrospective cohort study within Kaiser Permanente Northern California and identified 1015 adults with end-stage renal disease who underwent an index coronary revascularization procedure between 1996 and 2008. We used logistic regression analysis and obtained odds ratios for the primary predictor age when age was a. dichotomized at at a cutoff of ≥ 65 years b. categorized as ≤ 55 (reference), 55-64, 65-74, & ≥ 75 years c. modeled as a continuous predictor with a clinically relevant scale (every 5 years ) and d. when age was transformed to a restricted cubic spline (RCS) with four knots. We chose to report in this abstract only the primary outcome repeat revascularization due to the ease in graphically appreciating the various modeling strategies noted above. Results: For the primary outcome repeat revascularization, the unadjusted odds ratio for age ≥ 65 years was 0.64 (95% CI: 0.49-0.82). Categorized age 55-64 years was 0.73 (95% CI: 0.55-0.99), 65-74 years was 0.46 (95% CI: 0.33-0.64), and ≥ 75 years was 0.75 (95% CI: 0.50-1.14), pFigure 1 is a graphical representation of the four different modeling methods of age as noted above. Conclusions: Qualitatively, these four modeling strategies led to different conclusions. When age was dichotomized, there was a significant loss of information. Linearized age did not sufficiently address either the increase in repeat revascularization at both ends of age nor the nadir but appeared to have an adequate fit. Categorized age was able to note the nadir in repeat revascularization around the age of 65 years with a subsequent increase at both ends but the current age categories underrepresented the increased revascularization in the early years. Age transformed to a RCS was visually appealing but lacked adequate quantitative assessment. Therefore, when modeling a continuous variable such as age, there is an imperative to balance the issues of overfitting, residual confounding, flexibility and appropriate interpretation.

Randomized clinical trials comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) have largely excluded patients with chronic kidney disease (CKD), leading to uncertainty about the optimal coronary revascularization strategy. We sought to test the hypothesis that an initial strategy of CABG would be associated with lower risks of long-term mortality and cardiovascular morbidity compared with PCI for the treatment of multivessel coronary heart disease in the setting of CKD.We created a propensity score-matched cohort of patients aged ≥30 years with no prior dialysis or renal transplant who received multivessel coronary revascularization between 1996 and 2008 within a large integrated health care delivery system in northern California. We used extended Cox regression to examine death from any cause, acute coronary syndrome, and repeat revascularization.Coronary artery bypass grafting was associated with a significantly lower adjusted rate of death than PCI across all strata of estimated glomerular filtration rate (eGFR) (in mL/min per 1.73 m(2)): the adjusted hazard ratio (HR) was 0.81, 95% CI 0.68 to 1.00 for patients with eGFR ≥60; HR 0.73 (CI 0.56-0.95) for eGFR of 45 to 59; and HR 0.87 (CI 0.67-1.14) for eGFR45. Coronary artery bypass grafting was also associated with significantly lower rates of acute coronary syndrome and repeat revascularization at all levels of eGFR compared with PCI.Among adults with and without CKD, multivessel CABG was associated with lower risks of death and coronary events compared with multivessel PCI.

Introduction: Randomized clinical trials comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) have generally excluded patients with chronic kidney disease, and observational comparisons have been inconclusive. Hypothesis: We examined whether initial revascularization with CABG is associated with lower risks of death and coronary events compared with PCI among patients with chronic kidney disease and multivessel coronary disease. Methods: We identified adults aged ≥30 years in Kaiser Permanente of Northern California with multivessel coronary disease who underwent initial revascularization between 1996 and 2008. Patients were followed for the outcomes of death, acute coronary syndrome, or repeat revascularization until December 31, 2008. We calculated the estimated glomerular filtration rate (eGFR, in mL/min per 1.73 m2) using the CKD-EPI equation and stratified the cohort into three eGFR categories: ≥60, 45-59, and Results: Among 22,361 adults receiving CABG (n=16,219) or PCI (n=6142), 26% had baseline eGFR 45-59, and 15% had baseline eGFR Conclusions: Among adults with chronic kidney disease and multivessel coronary disease, initial revascularization with CABG is associated with lower risks of death and coronary events compared with PCI. Our findings support conducting adequately-powered randomized clinical trials comparing coronary revascularization strategies specifically in patients with chronic kidney disease.

Background: Platelet inhibition after percutaneous coronary intervention (PCI) reduces the risk of myocardial infarction (MI) but increases the risk of bleeding. Periprocedural bleeding is associated with an increased short-term risk of adverse outcomes. However, the prognostic significance of non-periprocedural bleeds (i.e., those occurring after hospital discharge) has not been systematically studied in community-based populations. The relative impact of a non-periprocedural bleed versus a subsequent MI on long-term mortality could help define the net clinical benefit of newer, more potent antiplatelet and antithrombotic strategies. Methods: We conducted a retrospective cohort study of all patients ≥ 30 years without known coronary disease who underwent a PCI between 1996-2008 within Kaiser Permanente of Northern California. Patients were followed for subsequent MI or hospitalization for bleeding between 7 to 365 days after discharge from the index hospitalization. The primary outcome was all-cause mortality, which was ascertained from health-plan, state, and Social Security Administration death files. We evaluated the independent prognostic value of post-discharge MI or bleed using a multivariable Cox regression model that adjusted for demographics, clinical history (including hypertension, diabetes, dyslipidemia, and a history of MI or bleed prior to, during, or within 7 days after index hospitalization), kidney function, and longitudinal medication exposure. Results: Among 32,906 adults who survived the index PCI, 530 patients had a bleed and 991 had an MI between 7 and 365 days after discharge from the index hospitalization. Patients who suffered a bleed were older and more likely to be female and have hypertension, peripheral artery disease, chronic kidney disease or history of bleeding. They were also more likely to receive warfarin, but antiplatelet therapy use was similar in the two groups. During a mean 4.42 years of follow-up, we observed 4,048 deaths (164 in patients who had a bleed, and 315 in patients who had an MI). Compared with patients who did not have a bleed or an MI, patients who had a hospitalized bleed had a significantly increased risk of death (hazard ratio [HR], 1.65; 95% CI: 1.33-2.04). The increased hazard of long-term mortality associated with bleeding was similar to that associated with an MI during follow-up (HR, 1.87; 95% CI: 1.58-2.22), and persisted after adjustment for antiplatelet and antithrombotic therapy use - suggesting that it could not be fully explained by the differential use of these therapies among patients who bleed. Conclusions: In a large, diverse, community-based sample of adults undergoing PCI, non-periprocedural bleeding was associated with a significant increase in long-term mortality, which was similar in magnitude to that associated with an MI, and was not fully explained by the differential use of antiplatelet and antithrombotic drugs. Our results underscore the significant negative prognostic implications of bleeding, and emphasize the careful evaluation of the long-term net clinical benefit of evolving antiplatelet and antithrombotic strategies in the management of coronary disease.

Background. Pooled analyses of randomized trials comparing CABG and PCI suggest a modest mortality benefit with CABG in selected patients (adjusted hazard ratio 0.70). However, limited data exist for patients treated in typical clinical practice, and most previously published studies were underpowered to examine variation in outcomes by patient characteristics. We evaluated the comparative effectiveness of CABG vs. PCI in patients with multivessel coronary artery disease, overall and in target patient subgroups. Methods. We conducted a retrospective cohort study of adults receiving isolated CABG or PCI for multivessel coronary disease between 1996-2008 within Kaiser Permanente of Northern California, a large, integrated healthcare delivery system. Demographic characteristics, cardiovascular history, comorbidities and longitudinal cardiovascular drug exposure were ascertained from health plan hospitalization, outpatient, laboratory and pharmacy databases. Deaths through 2008 were identified from health plan, state death certificate, and Social Security Administration death files. Results. In 28,735 adults with multivessel coronary disease receiving CABG (n=20,664) or PCI (n=8,071), those receiving CABG were more likely to be older and male. In multivariable extended Cox regression analysis that adjusted for potential time-updated confounders, CABG was associated with lower rates of death from any cause (adjusted hazard ratio 0.83, 95% CI: 0.76-0.90) compared with PCI. Compared with PCI, CABG was associated with significantly lower adjusted rates for death in those with and without diabetes, in those aged ≥75 years but not in those 65-74 or Conclusions. In a large, diverse, community-based cohort of patients with multivessel coronary disease, CABG was independently associated with lower rates of death compared with PCI, but less so than seen in RCTs. Results further varied by patient characteristics, suggesting the need to re-evaluate selection of revascularization type in patients with symptomatic multivessel coronary disease.

In patients with normal renal function recent trial and registry data suggests that mortality between men and women are similar after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). In contrast, there is an incomplete understanding of gender differences in the end

Limited data exists about recent temporal trends of outcomes after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the growing population of end-stage renal disease (ESRD) patients receiving chronic dialysis. Within Kaiser Permanente Northern California, a

Background Platelet inhibition after percutaneous coronary intervention (PCI) reduces the risk of myocardial infarction (MI) but increases the risk of bleeding. MIs and bleeds during the index hospitalization for PCI are known to negatively affect long-term outcomes. The impact of spontaneous bleeding occurring after discharge on long-term mortality is unknown. Objectives This study sought to examine, in a real-world cohort, the association between spontaneous major bleeding or MI after PCI and long-term mortality. Methods We conducted a retrospective cohort study of patients ≥30 years of age who underwent a PCI between 1996 and 2008 in an integrated healthcare delivery system. We used extended Cox regression to examine the associations of spontaneous bleeding and MI with all-cause mortality, after adjustment for time-updated demographics, comorbidities, periprocedural events, and longitudinal medication exposure. Results Among 32,906 patients who had a PCI and survived the index hospitalization, 530 had bleeds and 991 had MIs between 7 and 365 days post-discharge. There were 4,048 deaths over a mean follow-up of 4.42 years. The crude annual death rate after a spontaneous bleed (9.5%) or MI (7.6%) was higher than among patients who experienced neither event (2.6%). Bleeding was associated with an increased rate of death (adjusted hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.30 to 2.00), similar to that after an MI (HR: 1.91; 95% CI: 1.62 to 2.25). The association of bleeding with death remained significant after additional adjustment for the longitudinal use of antiplatelet agents. Conclusions Spontaneous bleeding after a PCI was independently associated with higher long-term mortality, and conveyed a risk comparable to that of an MI during follow-up. This tradeoff between efficacy and safety bolsters the argument for personalizing antiplatelet therapy after PCI on the basis of the patient’s long-term risk of both thrombotic and bleeding events.

ObjectivesThis study sought to examine the effectiveness of clopidogrel in real-world, medically managed patients with unstable angina (UA) or non–ST-segment elevation myocardial infarction (NSTEMI).BackgroundAlthough clinical trials have demonstrated the efficacy of clopidogrel to reduce cardiovascular (CV) morbidity and mortality in medically managed patients with UA or NSTEMI, the effectiveness of clopidogrel in actual clinical practice is less certain.MethodsA retrospective cohort study was conducted of Kaiser Permanente Northern California members without known coronary artery disease or prior clopidogrel use who presented with UA or NSTEMI between 2003 and 2008 and were medically managed (i.e., no percutaneous coronary intervention or coronary artery bypass grafting during the index hospitalization or within 7 days post-discharge). Over 2 years of follow-up, we measured the association between clopidogrel use and all-cause mortality, hospital stay for MI, and a composite endpoint of death or MI using propensity-matched multivariable Cox analyses.ResultsWe identified 16,365 patients with incident UA (35%) or NSTEMI (65%); 36% of these patients were prescribed clopidogrel within 7 days of discharge. In 8,562 propensity score–matched patients, clopidogrel users had lower rates of all-cause mortality (8.3% vs. 13.0%; p < 0.01; adjusted hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.54 to 0.72) and the composite of death or MI (13.5% vs. 17.4%; p < 0.01; HR: 0.74, CI: 0.66 to 0.84), but not MI alone (6.7% vs. 7.2%; p = 0.30; HR: 0.93, CI: 0.78 to 1.11), compared with nonusers of clopidogrel. The association between clopidogrel use and the composite of death or MI was significant only among patients presenting with NSTEMI (HR: 0.67; CI: 0.59 to 0.76; pint < 0.01), not among those presenting with UA (HR: 1.25; CI: 0.94 to 1.67).ConclusionsIn a large, community-based cohort of patients who were medically managed after UA/NSTEMI, clopidogrel use was associated with a lower risk of death and MI, particularly among patients with NSTEMI.

Few studies have quantified resource utilization or costs after percutaneous coronary intervention (PCI) on a population level. Understanding variation in resource use is necessary to improve the quality of care for this population. We conducted a retrospective cohort study of patients >20 years