Gregory A. Nichols

Key Points: Onset of any new cardio-renal-metabolic condition drove substantial increase in health care costs. Overall costs increased by $10,316 (130%) when CKD developed, $6789 (84%) for type 2 diabetes, $21,573 (304%) for atherosclerotic cardiovascular disease, and $36,522 (475%) for heart failure. However, as a result of prediagnosis costs being higher as more conditions were present, the percentage increases in costs associated with incidence were lower when more prevalent conditions existed. Background: The cardio-renal-metabolic (CRM) syndrome is a constellation of conditions which includes atherosclerotic cardiovascular disease, heart failure (HF), CKD, and type 2 diabetes. The economic consequences of developing each of these comorbidities in the context of the others have not been studied. Methods: We used the electronic medical records of Kaiser Permanente Northwest to identify 387,985 members aged 18 years or older who had a serum creatinine measured between 2005 and 2017. Patients were followed through 2019. We used a statistical approach that assesses time dependency for continuous measures; the total observation period for each patient was divided into quarters (91-day increments), and each patient contributed a record for every quarter in which they were members of the health plan. CRM status was determined for each quarter. Results: The incremental annualized cost of each of these chronic diseases was similar regardless of which other conditions were present when the new condition developed. Overall costs increased by $10,316 (130%) when CKD developed, $6789 (84%) for type 2 diabetes, $21,573 (304%) for atherosclerotic cardiovascular disease, and $36,522 (475%) for HF. However, as a result of prediagnosis costs being higher as more conditions were present, the percentage increases in costs associated with incidence were lower when more prevalent conditions existed. Conclusions: Onset of any new CRM condition drove substantial increase in health care costs. Our findings indicate a clear interplay of CRM conditions and emphasize the need for better simultaneous prevention and management of these disease states to reduce the economic burden on health care systems.

Background: The cardiometabolic syndrome focuses on the association between type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), whereas the cardiorenal syndrome focuses on the association between chronic kidney disease (CKD) and heart failure (HF). Consideration of these two syndromes as a single entity has not been well described. Methods: We used the electronic medical records of Kaiser Permanente Northwest to identify 387,985 members aged 18+ years with a serum creatinine measured from 2005 to 2017. If the estimated glomerular filtration rate was 2 , we required a second confirmatory measurement 3–12 months later. Patients were followed through 2019. We calculated the age- and gender-adjusted incidence and progression of CKD per 1000 person-years using generalized estimating equations. We used Cox proportional hazard models to assess the time-dependent effect of each condition on incidence of the other conditions. Results: CKD incidence rates were highest in patients with T2DM, ASCVD, and HF (27.0 per 1000 person-years [95% confidence interval (CI) 24.8–29.4] vs. 5.9 [5.8–6.0] in patients with none of these conditions). Similar results were obtained for CKD progression (309.0, 283.9–336.4 for all three conditions vs. 147.9, 143.3–152.4 for no condition). In time-dependent models, all three conditions were independently associated with CKD incidence, being highest for HF (hazard ratio 2.14, 95% CI 2.07–2.21). All relationships between CKD, T2DM, ASCVD, and HF were significant and bidirectional. Conclusions: The presence of CKD, T2DM, HF, and ASCVD each conveys risk on the others. A cardiometabolic renal syndrome comprising these conditions may be an important disease entity that requires a comprehensive treatment approach.

Introduction Type 2 diabetes (T2D) is a common condition that, if left untreated or poorly managed, can lead to adverse microvascular and macrovascular complications. We estimated the prevalence and incidence of microvascular and macrovascular complications among patients newly diagnosed with T2D within a US integrated healthcare system. Research design and methods We conducted a retrospective cohort study among patients newly diagnosed with T2D between 2003 and 2014. We evaluated 13 complications, including chronic kidney disease (CKD), cardiovascular disease (CVD), and all-cause mortality through 2018. Multivariable Cox proportional hazards models were used to study factors associated with complications. Results We identified 135 199 patients with incident T2D. The mean age was 58 years, and 48% were women. The prevalence of CKD was the highest of the complications at the time of T2D diagnosis (prevalence=12.3%, 95% CI 12.2% to 12.5%), while the prevalence of CVD was among the lowest at 3.3% (95% CI 3.2% to 3.3%). The median time to incidence of a T2D complication ranged from 3.0 to 5.2 years. High incidence rates (95% CI) of T2D complications included peripheral neuropathy (26.9, 95% CI 26.5 to 27.3 per 1000 person-years (PY)), CKD (21.2, 95% CI 20.9 to 21.6 per 1000 PY), and CVD (11.9, 95% CI 11.7 to 12.2 per 1000 PY). The trend of 5-year incidence rates of T2D complications by diagnosis year decreased over time (p valueConclusion Though incidence rates of T2D complications were lower in more recent years (2010–2014), a significant proportion of patients had complications at T2D diagnosis. Earlier preventive therapies as well as managing modifiable factors may help delay the development and progression of T2D complications.

Background: Recorded diagnoses of acute pancreatitis (AP) are often inaccurate resulting in limited utility for case identification in large data sources, especially where electronic medical records (EMR) are not available. Our objectives were to validate diagnoses of AP and to identify an algorithm using additional data to enhance the identification of AP cases in different data sources.Methods: We randomly sampled 550 persons with an AP diagnosis from inpatient data or outpatient or emergency department diagnoses immediately preceding a hospitalization and 150 negative controls with a differential diagnosis (cholangitis or cholecystitis). We conducted an EMR review to confirm cases of AP and used logistic regression to develop EMR‐based and claims‐based algorithms to identify confirmed AP cases with variables typically available in electronic data sources. Algorithm performance was assessed using the C statistic, sensitivity, specificity, and positive and negative predictive value.Results: Of the 550 patients with an AP diagnosis, 467 (84.9%) were confirmed cases. An AP diagnosis alone had high sensitivity (98.9%), modest specificity (63.6%), and a C statistic of 0.813. An EMR‐based model using an AP diagnosis, body mass index ≥30 kg/m², a serum lipase >3 times upper limit of normal and diabetes attained a C‐statistic of 0.914. A claims‐based model attained a C‐statistic of 0.892 using an AP diagnosis and dichotomous variables for whether a serum lipase test and/or an abdominal ultrasound was performed.Conclusions: Our simple algorithms increased the accuracy of identification of AP cases providing widespread applicability to epidemiological and drug safety studies.

Patients with type 2 diabetes mellitus (T2D) are at risk of various comorbidities. We investigated the timing of incident T2D complications over the course of 15 years and clinical characteristics associated with those complications in a large U.S. integrated healthcare system. We identified incident T2D between 2003-2014 with a validated algorithm using electronic health records. T2D complications included micro- and macro-vascular diseases, depression, and all-cause mortality. We calculated incidence rates per 1000 person-years and median time to developing each complication through 2018. Multivariable Poisson regression models were used to investigate factors associated with early T2D complications defined as shorter than the median time to incidence. We identified 135,199 patients with newly diagnosed T2D and followed them for a median six years [mean age 58 years, 48% female, 36% White, 35% Hispanic, 12% Black, 13% Asian]. Median times to incidence of depression, peripheral vascular disease, stable angina, and chronic kidney disease (CKD) were shorter than median times to incidence of lower extremity amputation, stroke, and heart failure (Table). Having hypertension and lower eGFR were associated with shorter time to CKD whereas male was associated with shorter time to composite cardiovascular events. Older age and a higher comorbidity score were associated with shorter time to both. Disclosure: J. An: Research Support; Self; Merck & Co., Inc., Novartis AG. G.A. Nichols: Research Support; Self; Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Merck & Co., Inc. L. Qian: None. Z. Li: None. M.A. Munis: None. R. Wei: None. T. Harrison: None. T. Weiss: Employee; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Menarini Group. K. Reynolds: Research Support; Self; CSL Behring, Merck & Co., Inc., National Institutes of Health, Novartis Pharmaceuticals Corporation.

An amendment to this paper has been published and can be accessed via the original article.

Background: Studies of progression of kidney dysfunction typically focus on renal replacement therapy or percentage decline in estimated glomerular filtration rate (eGFR) as outcomes. Our aim was to compare real-world patients with and without T2D to estimate progression from and to clinically defined categories of kidney disease and all-cause mortality. Methods: This was an observational cohort study of 31,931 patients with and 33,201 age/sex matched patients without type 2 diabetes (T2D) who had a serum creatinine and urine albumin-to-creatinine ratio (UACR) or dipstick proteinuria (DP) values. We used the first available serum creatinine value between 2006 and 2012 to calculate baseline eGFR and categorized them and the corresponding UACR/DP values using the Kidney Disease Improving Global Outcomes (KDIGO) categories. To assess our primary outcomes, we extracted probabilities of eGFR progression or mortality from life-table analyses and conducted multivariable Cox regression analyses of relative risk adjusted for age, sex, race/ethnicity, smoking, ischemic heart disease, heart failure, and use of renal-angiotensin-aldosterone system inhibitors. Results: Patterns of eGFR decline were comparable among patients with vs. without T2D with larger percentage declines at higher albuminuria levels across all eGFR categories. eGFR decline was generally larger among T2D patients, particularly in those with severely increased albuminuria. Across all CKD categories, risk of progression to the next higher category of eGFR was substantially increased with increasing albuminuria. For example, the risk was 23.5, 36.2, and 65.1% among T2D patients with eGFR 30–59 ml/min/1.73m² and UACR < 30, 30–299, and > 300 mg/dL, respectively (p < 0.001). Other comparisons were similarly significant. Among patients with low eGFR and normal to mildly increased albuminuria, the relative risk was up to 8-fold greater for all-cause mortality compared with the non-CKD subgroup (eGFR> 60 ml/min/1.73m² with normal to mildly increased albuminuria). Conclusions: Presence of albuminuria was associated with accelerated eGFR decline independent of T2D. Risk for adverse outcomes was remarkably high among patients with CKD and normal to mildly increased albuminuria levels. Independent of T2D or albuminuria, a substantial risk for adverse outcomes exists for CKD patients in a routine care setting.

The outside front cover image is based on the Review Article Risk of Cardiovascular Events in Patients with Hypertriglyceridemia: A Review of Real‐World Evidence by Peter Paul Toth, NATHAN D. WONG, GREGORY, A. NICHOLS et al., https://doi.org/10.1111/dom.13921 . image