Global assessment improves risk stratification for major adverse cardiac events across a wide range of triglyceride levels: Insights from the KP REACH study.

OBJECTIVE: Patients with risk factors for or established atherosclerotic cardiovascular disease (ASCVD) remain at high risk for subsequent ischemic events despite statin therapy. Triglyceride (TG) levels may contribute to residual ASCVD risk, and the performance of global risk assessment calculators across a broad range of TG levels is unknown. METHODS: We performed a retrospective cohort study of Kaiser Permanente Northern California members aged ≥45 years with ≥1 ASCVD risk factor (primary prevention cohort) or established ASCVD (secondary prevention cohort) between 2010 and 2017 who were receiving statin therapy and had a low-density lipoprotein cholesterol between 41-100 mg/dL. Global ASCVD risk assessment was performed using both the Kaiser Permanente ASCVD Risk Estimator (KPARE) and the ACC/AHA ASCVD Pooled Cohort Equation (PCE). Outcomes included major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, or peripheral artery disease, and expanded MACE (MACE + coronary revascularization + hospitalization for unstable angina). RESULTS: Among 373,389 patients in the primary prevention cohort, median TG was 122 mg/dL (IQR 88-172 mg/dL) and there were 0.2 MACE events and 0.3 expanded MACE events per 100-person years. Among 97,832 patients in the secondary prevention cohort, median TG level was 116 mg/dL (IQR 84-164 mg/dL) and there were 9.6 MACE events and 22.0 expanded MACE events per 100-person years. KPARE and the ACC/AHA PCE stratified patients for MACE and expanded MACE over the entire range of TGs. CONCLUSION: In a cohort receiving statin therapy for primary or secondary prevention, we found global assessment further improves risk stratification for initial and/or recurrent ASCVD events irrespective of baseline TG level.

Risk Factors for Recurrent Acute Kidney Injury in a Large Population-Based Cohort.

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) has numerous sequelae. Repeated episodes of AKI may be an important determinant of adverse outcomes, including chronic kidney disease and death. In a population-based cohort study, we sought to determine the incidence of and predictors for recurrent AKI. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 38,659 hospitalized members of Kaiser Permanente Northern California who experienced an episode of AKI from 2006 to 2013. PREDICTORS: Demographic, clinical, and laboratory data, including baseline kidney function, proteinuria, hemoglobin level, comorbid conditions, and severity of AKI. OUTCOMES: Incidence and predictors of recurrent AKI. ANALYTICAL APPROACH: Multivariable Cox proportional hazard regression. RESULTS: 11,048 (28.6%) experienced a second hospitalization complicated by AKI during follow-up (11.2 episodes/100 person-years), with the second episode of AKI occurring a median of 0.6 (interquartile range, 0.2-1.9) years after the first hospitalization. In multivariable analyses, older age, black race, and Hispanic ethnicity were associated with recurrent AKI, along with lower estimated glomerular filtration rate, proteinuria, and anemia. Concomitant conditions, including heart failure, acute coronary syndrome, diabetes, and chronic liver disease, were also multivariable predictors of recurrent AKI. Those who had higher acuity of illness during the initial hospitalization were more likely to have recurrent AKI, but greater AKI severity of the index episode was not independently associated with increased risk for recurrent AKI. In multivariable analysis of matched patients, recurrent AKI was associated with an increased rate of death (HR, 1.66; 95% CI, 1.57-1.77). LIMITATIONS: Analyses were based on clinically available data, rather than protocol-driven timed measurements of kidney function. CONCLUSIONS: Recurrent AKI is a common occurrence after a hospitalization complicated by AKI. Based on routinely available patient characteristics, our findings could facilitate identification of the subgroup of patients with AKI who may benefit from more intensive follow-up to potentially avoid recurrent AKI episodes.

Risk of Type 2 Diabetes Mellitus following Gestational Diabetes Pregnancy in Women with Polycystic Ovary Syndrome.

BACKGROUND: This study examines gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS) and the risk of type 2 diabetes mellitus (DM) following GDM pregnancy. METHODS: A cohort of 988 pregnant women with PCOS who delivered during 2002-2005 was examined to determine the prevalence and predictors of GDM, with follow-up through 2010 among those with GDM to estimate the risk of DM. RESULTS: Of the 988 pregnant women with PCOS, 192 (19%) developed GDM. Multivariable predictors of GDM included older age, Asian race, prepregnancy obesity, family history of DM, preconception metformin use, and multiple gestation. Among women with PCOS and GDM pregnancy, the incidence of DM was 2.8 (95% confidence interval (CI) 1.9-4.2) per 100 person-years and substantially higher for those who received pharmacologic treatment for GDM (6.6 versus 1.5 per 100 person-years, p < 0.01). The multivariable adjusted risk of DM was fourfold higher in women who received pharmacologic treatment for GDM (adjusted hazard ratio 4.1, 95% CI 1.8-9.6). The five-year incidence of DM was 13.1% overall and also higher in the pharmacologic treatment subgroup (27.0% versus 7.1%, p < 0.01). CONCLUSIONS: The strongest predictors of GDM among women with PCOS included Asian race and prepregnancy obesity. Pharmacologic treatment of GDM is associated with fourfold higher risk of subsequent DM.

Effectiveness and safety of digoxin among contemporary adults with incident systolic heart failure.

BACKGROUND: Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF. METHODS AND RESULTS: We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent ß-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25-2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82-1.34). Results were similar in analyses stratified by sex and ß-blocker use. CONCLUSIONS: Digoxin use in patients with incident systolic HF was independently associated with a higher risk of death but no difference in HF hospitalization.

Comparative effectiveness of different beta-adrenergic antagonists on mortality among adults with heart failure in clinical practice.

BACKGROUND: Randomized trials have demonstrated the efficacy of selected beta-blockers in systolic heart failure, but the comparative effectiveness of different beta-blockers in practice is poorly understood. METHODS: We compared mortality associated with different beta-blockers following hospitalization for heart failure between 2001 and 2003. Longitudinal exposure to beta-blockers was ascertained from pharmacy databases. Patient characteristics and other medication use were identified from administrative, hospitalization, outpatient, and pharmacy databases. Death was identified from administrative, state mortality, and Social Security Administration databases. Multivariate Cox regression was used to examine the association between different beta-blockers and death. RESULTS: Among 11 326 adults surviving a hospitalization for heart failure, 7976 received beta-blockers (atenolol, 38.5%; metoprolol tartrate, 43.2%; carvedilol, 11.6%; and other, 6.7%) during follow-up. The rate (per 100 person-years) of death during the 12 months after discharge varied by exposure and type of beta-blocker (atenolol, 20.1; metoprolol tartrate, 22.8; carvedilol, 17.7; and no beta-blockers, 37.0). After adjustment for confounders and the propensity to receive carvedilol, the risk of death compared with atenolol was higher for metoprolol tartrate (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.34) and no beta-blockers (HR, 1.63; 95% CI, 1.44-1.84) but was not significantly different for carvedilol (HR, 1.16; 95% CI, 0.92-1.44). CONCLUSIONS: Compared with atenolol, the adjusted risks of death were slightly higher with shorter-acting metoprolol tartrate but did not significantly differ for carvedilol in adults with heart failure. Our results should be interpreted cautiously and they suggest the need for randomized trials within real-world settings comparing a broader spectrum of beta-blockers for heart failure.