Incidence of depression in patients with cardiovascular disease and type 2 diabetes: a nationwide cohort study.

BACKGROUND: Estimating how type 2 diabetes (T2D) affects the rate of depression in cardiovascular disease (CVD) can help identify high-risk patients. The aim is to investigate how T2D affects the rate of depression according to specific subtypes of CVD. METHODS: Incident CVD patients, free of psychiatric disease, with and without T2D, were included from nationwide registries between 2010 and 2020. We followed patients from CVD diagnosis until the first occurrence of depression, emigration, death, 5 years, or end of study (December 31, 2021). We used time-dependent Poisson regression to estimate the incidence rates and rate ratios (IRR) of depression following subtypes of CVD with and without T2D. The model included age, sex, comorbidities, calendar year, T2D duration, educational level, and living situation as covariates. RESULTS: A total of 165,096 patients were included; 45,845 had a myocardial infarction (MI), 63,691 had a stroke, 19,959 had peripheral artery disease (PAD), 35,568 had heart failure (HF), and 979 were diagnosed with 2 or more CVD subtypes (= > 2 CVD's). Baseline T2D in each CVD subtype ranged from 11 to 17%. The crude incidence rate of depression per 1000 person-years (95% confidence intervals) was: MI + T2D: 131.1 (109.6;155.6), MI: 82.1 (65.3;101.9), stroke + T2D: 287.4 (255.1;322.6), stroke: 222.4(194.1;253.6), PAD + T2D: 173.6 (148.7;201.4), PAD:137.5 (115.5;162.5), HF + T2D: 244.3 (214.6;276.9), HF: 199.2 (172.5;228.9), = > 2 CVD's + T2D: 427.7 (388.1;470.2), = > 2 CVD's: 372.1 (335.2;411.9). The adjusted IRR of depression in MI, stroke, PAD, HF, and = > 2 CVD's with T2D compared to those free of T2D was: 1.29 (1.23;1.35), 1.09 (1.06;1.12), 1.18 (1.13;1.24), 1.05 (1.02;1.09), and 1.04 (0.85;1.27) (p-value for interaction < 0.001). CONCLUSION: The presence of T2D increased the rate of depression differently among CVD subtypes, most notable in patients with MI and PAD.

Risk of first-time major cardiovascular event among individuals with newly diagnosed type 2 diabetes: data from Danish registers.

AIMS/HYPOTHESIS: We aimed to examine whether individuals with initial omission of glucose-lowering drug treatment (GLDT), including those achieving initial remission of type 2 diabetes, may experience a higher risk of major adverse cardiovascular events (MACE) compared with well-controlled individuals on GLDT after a new type 2 diabetes diagnosis in real-world clinical practice. Furthermore, we examined whether a higher risk could be related to lower initiation of statins and renin-angiotensin system inhibitors (RASi). METHODS: In this cohort study, we used Danish registers to identify individuals with a first measured HbA1c between 48 and 57 mmol/mol (6.5-7.4%) from 2014 to 2020. Six months later, we divided participants into four groups according to GLDT and achieved HbA1c (<48 vs ≥48 mmol/mol [6.5%]): well-controlled and poorly controlled on GLDT; remission and persistent type 2 diabetes not on GLDT. We reported how much the standardised 5 year risk of MACE could be reduced for each group if initiation of statins and RASi was the same as in the well-controlled group on GLDT. RESULTS: We included 14,221 individuals. Compared with well-controlled participants on GLDT, the 5 year standardised risk of MACE was higher in the three other exposure groups: by 3.3% (95% CI 1.6, 5.1) in the persistent type 2 diabetes group not on GLDT; 2.0% (95% CI 0.4, 3.7) in the remission group not on GLDT; and 3.5% (95% CI 1.3, 5.7) in the poorly controlled group on GLDT. Fewer individuals not on GLDT initiated statins and RASi compared with individuals on GLDT. If initiation of statins and RASi had been the same as in the well-controlled group on GLDT, participants not on GLDT could have reduced their risk of MACE by 2.1% (95% CI 1.2, 2.9) in the persistent type 2 diabetes group and by 1.1% (95% CI 0.4, 1.9) in the remission group. CONCLUSIONS/INTERPRETATION: Compared with well-controlled individuals on GLDT, individuals not on initial GLDT had a higher 5 year risk of MACE, even among those achieving remission of type 2 diabetes. This may be related to lower use of statins and RASi.

Plasma concentration of orally administered amoxicillin and clindamycin in patients receiving haemodialysis.

OBJECTIVES: In the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD). However, data on plasma concentrations of these antibiotics during HD are sparse. This study aims to determine if the plasma concentration of amoxicillin and clindamycin is sufficient during HD after oral administration of amoxicillin and clindamycin at three different time intervals prior to the HD procedure. METHODS: Adult patients receiving chronic HD were investigated twice with an interval of at least 7 days starting with either a tablet of 500/125 mg amoxicillin/clavulanic acid or a tablet of 600 mg clindamycin. Patients were randomized to take the antibiotics either 30, 60 or 120 min prior to the HD procedure. Plasma antibiotic concentrations were measured at start, midway and at the end of HD. A lower threshold was set at 2.0 mg/L for amoxicillin and at 1.0 mg/L for clindamycin. In addition, a population pharmacokinetic (PK) analysis was performed, assessing PTA. RESULTS: In the amoxicillin cohort (n = 37), 84% of patients and 95% of all plasma amoxicillin concentrations were above or at the threshold throughout the dialysis procedure. In the clindamycin cohort (n = 33), all concentrations were above the threshold throughout the dialysis procedure. Further, in all patients, the mean plasma concentration of both amoxicillin and clindamycin across the HD period was well above the threshold. Finally, the PK model predicted a high PTA in the majority of patients. DISCUSSION: In patients on chronic HD, oral administration of amoxicillin/clavulanic acid (500/125 mg) or clindamycin (600 mg) within 30-120 min prior to HD leads to a sufficient prophylactic plasma concentration across the HD period.

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'.

Socioeconomic position and first-time major cardiovascular event in patients with type 2 diabetes: a Danish nationwide cohort study.

AIMS: The association between socioeconomic position and cardiovascular disease has not been well studied in patients with type 2 diabetes. We aimed to examine the association between socioeconomic position and first-time major adverse cardiovascular events (MACE) in patients with type 2 diabetes. METHODS AND RESULTS: Through the Danish nationwide registers, we identified all residents with newly diagnosed type 2 diabetes between 2012 and 2017. Based on sex-stratified multivariable cause-specific Cox regression models, we calculated the standardized absolute 5-year risk of the composite outcome of first-time myocardial infarction, stroke, or cardiovascular mortality (MACE) according to income quartiles. A total of 57 106 patients with type 2 diabetes were included. During 155 989 person years, first-time MACE occurred in 2139 patients. Among both men and women, income was inversely associated with the standardized absolute 5-year risk of MACE. In men, the 5-year risk of MACE increased from 5.7% [95% confidence interval (CI) 4.9-6.5] in the highest income quartile to 9.3% (CI 8.3-10.2) in the lowest income group, with a risk difference of 3.5% (CI 2.4-4.7). In women, the risk of MACE increased from 4.2% (CI 3.4-5.0) to 6.1% (CI 5.2-7.0) according to income level, with a risk difference of 1.9% (CI 0.8-2.9). CONCLUSION: Despite free access to medical care in Denmark, low-socioeconomic position was associated with a higher 5-year risk of first-time MACE in patients with incident type 2 diabetes. Our results suggest prevention strategies could be developed specifically for patients with low-socioeconomic position.

Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality: a cluster-randomized clinical trial (TRIAGE III).

BACKGROUND: Risk stratification of patients in the emergency department can be strengthened using prognostic biomarkers, but the impact on patient prognosis is unknown. The aim of the TRIAGE III trial was to investigate whether the introduction of the prognostic and nonspecific biomarker: soluble urokinase plasminogen activator receptor (suPAR) for risk stratification in the emergency department reduces mortality in acutely admitted patients. METHODS: The TRIAGE III trial was a cluster-randomized interventional trial conducted at emergency departments in the Capitol Region of Denmark. Eligible hospitals were required to have an emergency department with an intake of acute medical and surgical patients and no previous access to suPAR measurement. Three emergency departments were randomized; one withdrew shortly after the trial began. The inclusion period was from January through June of 2016 consisting of twelve cluster-periods of 3-weeks alternating between intervention and control and a subsequent follow-up of ten months. Patients were allocated to the intervention if they arrived in interventional periods, where suPAR measurement was routinely analysed at arrival. In the control periods suPAR measurement was not performed. The main outcome was all-cause mortality 10 months after arrival of the last patient in the inclusion period. Secondary outcomes included 30-day mortality. RESULTS: The trial enrolled a consecutive cohort of 16,801 acutely admitted patients; all were included in the analyses. The intervention group consisted of 6 cluster periods with 8900 patients and the control group consisted of 6 cluster periods with 7901 patients. After a median follow-up of 362 days, death occurred in 1241 patients (13.9%) in the intervention group and in 1126 patients (14.3%) in the control group. The weighted Cox model found a hazard ratio of 0.97 (95% confidence interval, 0.89 to 1.07; p = 0.57). Analysis of all subgroups and of 30-day all-cause mortality showed similar results. CONCLUSIONS: The TRIAGE III trial found no effect of introducing the nonspecific and prognostic biomarker suPAR in emergency departments on short- or long-term all-cause mortality among acutely admitted patients. Further research is required to evaluate how prognostic biomarkers can be implemented in routine clinical practice. TRIAL REGISTRATION: clinicaltrials.gov, NCT02643459 . Registered 31 December 2015.

MR-proADM as a Prognostic Marker in Patients With ST-Segment-Elevation Myocardial Infarction-DANAMI-3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) has demonstrated prognostic potential after myocardial infarction (MI). Yet, the prognostic value of MR-proADM at admission has not been examined in patients with ST-segment-elevation MI (STEMI). METHODS AND RESULTS: The aim of this substudy, DANAMI-3 (The Danish Study of Optimal Acute Treatment of Patients with ST-segment-elevation myocardial infarction), was to examine the associations of admission concentrations of MR-proADM with short- and long-term mortality and hospital admission for heart failure in patients with ST-segment-elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of MR-proADM was 0.64 nmol/L (25th-75th percentiles, 0.53-0.79). Within 30 days 23 patients (2.0%) died and during a 3-year follow-up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of MR-proADM was, in adjusted models, associated with an increased risk of 30-day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01-7.11; P=0.049), long-term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97-5.29; P<0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32-5.58; P=0.007). For 30-day and 3-year mortality, the area under the curve for MR-proADM was 0.77 and 0.78, respectively. For 3-year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85; P=0.02) after addition of MR-proADM. CONCLUSIONS: Elevation of admission MR-proADM was associated with long-term mortality and heart failure, whereas the association with short-term mortality was borderline significant. MR-proADM may be a marker of prognosis after ST-segment-elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models. CLINICAL TRIAL REGISTRATION: URL: http:/www.ClinicalTrials.gov/. Unique identifiers: NCT01435408 and NCT01960933.