Initiation of medical therapy for heart failure patients according to kidney function: a Danish nationwide study

Background: Use of medical therapies for heart failure (HF) patients with moderate kidney dysfunction is low. We hypothesized that lack of initiation of HF therapy reflects the clinicians’ reluctance in very elderly and frail patients more than kidney dysfunction itself. Methods: HF patients were identified from nationwide registers between 2014 and 2021. Information was obtained on eGFR, frailty status, and prescription of HF therapy. Patients were divided into three groups: normal kidney function (eGFR ≥ 60); moderate kidney dysfunction (GFR between 30 and 59); and severe kidney dysfunction (GFR < 30). Multivariate Cox models were used to study the association of eGFR, age, and frailty with use of HF therapy. Results: Of the 42,320 HF patients included those with lower eGFR were significantly older and frailer (median age 74.3 years and 37.8% frail). The crude initiation rate of all three drug classes decreased with decreasing eGFR in a stepwise fashion. After adjusting for age and frailty status, initiation of MRA decreased with decreasing kidney function (moderate kidney function HR 0.80(95% CI 0.77–0.84) and severe kidney function HR 0.24(0.21–0.27)). After adjusting for age and frailty status, initiation of RAS inhibitor and BB was not significantly lower for moderate kidney dysfunction (HR 0.97(0.93–1.02), and HR 1.06(0.97–1.16, respectively)). Initiation of RAS inhibitor was significantly lower for patients with severe kidney dysfunction, HR 0.45(0.41–0.50), but not for BB initiation HR 1.09(1.05–1.14). Conclusion: In a real-world HF cohort, patients with moderate and severe kidney dysfunction were associated with reduced use of MRA irrespective of age and frailty. Reduced use of RASi was associated with severe kidney dysfunction, whereas for patients with moderate kidney dysfunction, reduced use was mainly driven by aging and frailty. Reduced use of BB seemed to be primarily explained by aging and frailty

Impact of socioeconomic position on initiation of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes – a Danish nationwide observational study

BACKGROUND: Low socioeconomic position may affect initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucacon-like-peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D). We examined the association between socioeconomic position and initiation of SGLT-2i or GLP-1RA in patients with T2D at time of first intensification of antidiabetic treatment. METHODS: Through nationwide registers, we identified all Danish patients on metformin who initiated second-line add-on therapy between December 10, 2012, and December 31, 2020. For each time period (2012-2014, 2015-2017, and 2018-2020), we used multivariable multinomial logistic regression to associate disposable income, as proxy for socioeconomic position, with the probability of initiating a specific second-line treatment at time of first intensification. We reported probabilities standardised to the distribution of demographics and comorbidities of patients included in the last period (2018-2020). FINDINGS: We included 48915 patients (median age 62 years; 61·7% men). In each time period, high-income patients were more often men and had less comorbidities as compared with low income-patients. In each time period, the standardised probability of initiating a SGLT-2i or a GLP-1RA was significantly higher in the highest income group compared with the lowest: 11·4% vs. 9·5% (probability ratio [PR] 1·21, 95 % confidence interval [CI] 1·01-1·44) in 2012-2014; 22·6% vs. 19.6% (PR 1·15, CI 1·05-1·27) in 2015-2017; and 65·8% vs. 54·8% (PR 1·20, CI 1·16-1·24) in 2018-2020. The differences by income were consistent across multiple subgroups. INTERPRETATION: Despite a universal healthcare system, low socioeconomic position was consistently associated with a lower probability of initiating a SGLT-2i or a GLP-1RA. These disparities may widen the future socioeconomic gap in cardiovascular outcomes. FUNDING: The work was funded by unrestricted grants from ‘Region Sjaelland Den Sundhedsvidenskabelige Forskningsfond’ and ‘Murermester Lauritz Peter Christensen og hustru Kirsten Sigrid Christensens Fond’

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study

Background: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. Methods: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. Findings: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7–6·1) and median age across the three frailty groups was 71 years (64–79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88–0·94, p<0·0001; severely frail 0·75, 0·70–0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. Interpretation: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. Funding: Department of Cardiology, Herlev and Gentofte University Hospital. Translation: For the Danish translation of the abstract see Supplementary Materials section

Establishing post mortem criteria for the metabolic syndrome: an autopsy based cross-sectional study

Abstract Background Individuals who suffer from mental illness are more prone to obesity and related co-morbidities, including the metabolic syndrome. Autopsies provide an outstanding platform for the macroscopic, microscopic and molecular-biological investigation of diseases. Autopsy-based findings may assist in the investigation of the metabolic syndrome. To utilise the vast information that an autopsy encompasses to elucidate the pathophysiology behind the syndrome further, we aimed to both develop and evaluate a method for the post mortem definition of the metabolic syndrome. Methods Based on the nationwide Danish SURVIVE study of deceased mentally ill, we established a set of post mortem criteria for each of the harmonized criteria of the metabolic syndrome. We based the post mortem (PM) evaluation on information from the police reports and the data collected at autopsy, such as anthropometric measurements and biochemical and toxicological analyses (PM information). We compared our PM evaluation with the data from the Danish health registries [ante mortem (AM) information, considered the gold standard] from each individual. Results The study included 443 deceased individuals (272 male and 171 female) with a mean age of 50.4 (± 15.5) years and a median (interquartile range) post mortem interval of 114 (84–156) hours. We found no significant difference when defining the metabolic syndrome from the PM information in comparison to the AM information (P = 0.175). The PM evaluation yielded a high specificity (0.93) and a moderate sensitivity (0.63) with a moderate level of agreement compared to the AM evaluation (Cohen’s κ = 0.51). Neither age nor post mortem interval affected the final results. Conclusions Our model of a PM definition of the metabolic syndrome proved reliable when compared to the AM information. We believe that an appropriate estimate of the prevalence of the metabolic syndrome can be established post mortem. However, while neither the PM nor the AM information is exhaustive in terms of defining an individual’s health status, a superlative estimate may be obtained by combining the PM and the AM information. With this model, we open up the possibility of utilising autopsy data for future studies of the metabolic syndrome

Clinical cardiovascular phenotypes and the pattern of future events in patients with type 2 diabetes

Importance: Updated guidelines on diabetes recommend targeting sodium–glucose cotransporter-2 inhibitors (SGLT2i) at patients at risk of heart failure (HF) and glucagon-like peptide-1 receptor agonists (GLP1-RA) at those at greater risk of atherothrombotic events. Objective: We estimated the risk of different cardiovascular events in patients with type 2 diabetes (T2D) and newly established cardiovascular disease. Design, setting and participants: Patients with T2D and newly established cardiovascular disease from 1998 to 2016 were identified using Danish healthcare registers and divided into one of four phenotype groups: (1) HF, (2) ischemic heart disease (IHD), (3) transient ischemic stroke (TIA)/ischemic stroke, and (4) peripheral artery disease (PAD). The absolute 5-year risk of the first HF- or atherothrombotic event occurring after inclusion was calculated, along with the risk of death. Main outcomes and measures: The main outcome was the first event of either HF or an atherothrombotic event (IHD, TIA/ischemic stroke or PAD) in patients with T2D and new-onset cardiovascular disease. Results: Of the 37,850 patients included, 40% were female and the median age was 70 years. Patients with HF were at higher 5-year risk of a subsequent HF event (17.9%; 95% confidence interval (CI) 17.1–18.8%) than an atherothrombotic event (15.8%; 15.0–16.6%). Patients with IHD were at higher risk of a subsequent atherothrombotic event (24.6%; 23.9–25.3%) than developing HF, although the risk of HF was still substantial (10.6%; 10.2–11.1%). Conversely, patients with PAD were at low risk of developing HF (4.4%; 3.8–5.1%) but at high risk of developing an atherothrombotic event (15.9%; 14.9–17.1%). Patients with TIA/ischemic stroke had the lowest risk of HF (3.2%; 2.9–3.6%) and the highest risk of an atherothrombotic event (20.6%; 19.8–21.4). Conclusions: In T2D, a patient’s cardiovascular phenotype can help predict the pattern of future cardiovascular events