Aims: The aim of this study was to investigate the associations between symptomatic hearing loss (HL), neuropathy, and nephropathy in subjects with Type 2 diabetes mellitus (T2DM). Furthermore, the study evaluated whether HL was associated with chronic low-grade inflammation, assessed based on plasma levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), and explored potential sex-specific differences. Materials and Methods: We included 4245 subjects with T2DM from The Danish Centre for Strategic Research in Type 2 Diabetes cohort. Symptomatic HL was defined using ICD-10 codes. In 2016, a questionnaire was sent out to evaluate neuropathy using the Michigan Neuropathy Screening Instrument (MNSI ≥ 4). Nephropathy was defined as urinary albumin-to-creatinine ratio (UACR) >30 mg/g. Plasma levels of TNF-α, IL-6, and hsCRP were measured at enrolment from 2010 to 2016. Multivariable logistic regression was used, adjusting for covariates. Results: Neuropathy was significantly associated with HL (OR = 1.83, 95%CI [1.42, 2.35], p < 0.001), and the association was stronger in women (OR = 2.74 [1.81, 4.14], p < 0.001) compared to men (OR = 1.44 [1.04, 1.99], p < 0.05) (P-interaction = 0.020). No significant association was found between nephropathy and HL. Among inflammatory markers, only the highest tertile of TNF-α levels was significantly associated with HL compared to the lowest tertile (OR = 1.40 [1.07, 1.82], p < 0.05) without any sex interaction. Conclusions: In subjects with T2DM, neuropathy was associated with symptomatic HL, and the association seemed to be stronger in females. Among chronic low-grade inflammation markers, only TNF-α was significantly associated with symptomatic HL. Additionally, no significant association was found between nephropathy and HL.

Background and Aims The long-term prognostic value of standard C-reactive protein (CRP) in patients with myocardial infarction is unknown. Methods Using Danish nationwide registries, we identified patients with a first diagnosis of myocardial infarction from 2013 through 2020, who had a CRP measurement <=24 hours of index hospitalization. The primary outcome was death from any cause, and the secondary outcome was hospitalization or outpatient contact for new-onset heart failure. Absolute and relative risks for outcomes according to CRP quartiles at days 0-30 and 31-365 were calculated using multivariable Cox regression with average treatment effect modeling, adjusted for demographics and clinical features, including high-sensitivity troponin concentrations. Results A total of 29,035 patients with myocardial infarction were included. Median CRP was 4 mg/l, and quartile intervals were: quartile 1: <2.9 mg/l, quartile 2: 2.9 to <4 mg/l, quartile 3: 4 to <12 mg/l, and quartile 4: >=12 mg/l. At 0-30 days, 1,660 patients had died, and 1,861 died between days 31-365. The standardized absolute risk of death at both 0-30 and 31-365 days was lowest among patients in quartile 1 (0-30 days: 2.8%, 31-365 days: 4.1%) and highest among patients in quartile 4 (0-30 days: 9.7%, 31-365 days: 9.5%). The standardized relative risks of death increased in a stepwise fashion from quartile 2 to quartile 4 when using quartile 1 as the comparator. Similar findings were observed for heart failure. Conclusion Among patients with myocardial infarction, higher CRP concentrations were significantly associated with a higher risk of death and incident heart failure.

AIMS:We investigated longitudinal, bidirectional associations between objectively measured moderate to vigorous physical activity (MVPA), health-related quality of life (HRQoL), and emotional well-being (EWB) in individuals recently diagnosed with type 2 diabetes mellitus. METHODS:Participants were 972 adults. MVPA was assessed using accelerometry, HRQoL using the SF-12 (physical [PCS], mental [MCS]), and EWB using the WHO-5. A three-wave cross-lagged panel model tested associations, adjusting for age and sex. RESULTS:Baseline PCS predicted MVPA at 24 months (β = 0.124, p < 0.001), and PCS at 24 months predicted MVPA at 48 months (β = 0.146, p < 0.001). Baseline MCS predicted MVPA at 24 months (β = 0.116, p = 0.001), but not 48 months (β = -0.016, p = 0.653). Baseline EWB predicted MVPA at 24 months (β = 0.080, p = 0.023), but not 48 months (β = 0.068, p = 0.058). Baseline MVPA did not predict PCS at 24 months (β = 0.038, p = 0.184), but MVPA at 24 months predicted PCS at 48 months (β = 0.065, p = 0.024). MVPA did not predict MCS or EWB. CONCLUSIONS:HRQoL and EWB predicted subsequent MVPA, whereas MVPA showed limited and inconsistent effects on later HRQoL or EWB.

BACKGROUND:Registry-based randomised clinical trials are increasingly applied in clinical research, providing advantages in feasibility and data capture. However, registry-based data may introduce bias through misclassification or missing information. METHODS:In the BETAMI-DANBLOCK trial, 5,574 patients with myocardial infarction (MI) and no heart failure were randomised to beta-blocker or no beta-blocker therapy. The primary endpoint events (all-cause mortality, MI, ischemic stroke, heart failure, unplanned coronary revascularisation, and malignant ventricular arrhythmias) were identified from the Danish/Norwegian national patient registries, self-reported questionnaires, and medical records. All registry-identified events, except all-cause mortality, underwent blinded adjudication. We compared non-adjudicated and adjudicated events by calculating incidence rates and hazard ratios (HRs) for beta-blocker therapy versus controls. RESULTS:National registries captured 99.7% of primary endpoint events registered by self-report and medical records. Of the primary endpoint events identified through the registries, 75% were confirmed by adjudication (incidence rate 6.23 versus 4.43/100 person-years). The confirmation rate was lower during the first six months and varied by event type (from 92% for ischemic stroke to 45% for unplanned coronary revascularisations and heart failure). Estimated treatment effects were consistent for the primary endpoint with non-adjudicated and adjudicated events (HR 0.88, 95% confidence interval (CI): 0.78-0.98 and HR 0.85, 95% CI: 0.75-0.98, respectively), with no apparent differences across event types except for heart failure and revascularisation. CONCLUSION:Registry data provided effect estimates of beta-blockers comparable to adjudicated data. However, adjudication substantially reduced the number of cardiovascular endpoint events and event-specific misclassification appeared, particularly during the first months after the index-event.

AIMS:This study aimed to identify clinical factors associated with AVC in individuals with T2D. METHODS AND RESULTS:This cross-sectional study is a pre-specified substudy of the multicentre randomized Steno INTEN-CT trial (Clinical Trials-INTEN-CT). Participants were eligible if they had T2D without ischaemic heart disease and were aged between 55-69 years (men) or 60-74 years (women). All participants underwent non-contrast cardiac computed tomography. AVC was measured in Agatston Units and categorized as 0, 0-300, ≥ 300. Of the 4570 participants, 46% had AVC > 0. With increasing AVC, patients were older, predominantly males, and with significantly more comorbidities. In multivariable ordered logistic regression age (OR per SD 1.54, 95% CI 1.43-1.66), BMI (OR per SD 1.18, 95% CI 1.11-1.25), hypertension (OR 1.21, 95% CI 1.05-1.40), and chronic kidney disease (OR 1.18, 95% CI 1.03-1.36) were associated with higher AVC. Statin use was also associated with higher AVC (OR 1.50, 95% CI 1.27-1.78). Higher LDL cholesterol showed stronger associations with AVC in men than women (OR 1.39, 95% CI 1.24-1.56 vs. OR 1.16, 95% CI 1.02-1.31, P for interaction = 0.025). T2D severity (Haemoglobin A1c, T2D duration, and number of antidiabetic drugs) was not associated with AVC. CONCLUSION:In individuals with T2D without cardiovascular disease, AVC is prevalent in nearly half of all individuals. Higher AVC was associated with T2D-related comorbidities, but not T2D severity.

AIMS:This study aimed to evaluate the prognostic potential of circulating inflammatory biomarkers, specifically hsCRP, IL-6, TNF-α, and CD163, for predicting diabetic retinopathy (DR) in adults with recently diagnosed type 2 diabetes. METHODS:A prospective cohort of 3,363 individuals from the Danish Centre for Strategic Research in Type 2 Diabetes was followed prospectively (median follow-up of nine years). Baseline concentrations of four biomarkers were measured, and DR outcomes were assessed. Logistic regressions were used to evaluate associations with DR presence at baseline, while Cox regressions were used to analyze the development and progression of DR, adjusting for potential confounders, including HbA1c. RESULTS:No associations were observed between baseline concentrations of inflammatory biomarkers and DR presence, development, or progression over time. When comparing the highest quartile to the lowest quartile for a given biomarker in adjusted models, the hazard ratios (95% CI) for the development or progression of DR were: hsCRP 0.76 (0.55-1.03), IL-6 0.84 (0.62-1.14), TNF-α 1.03 (0.76-1.40), and CD163 0.84 (0.62-1.14). CONCLUSIONS:Our results indicate that systemic inflammatory biomarkers may not serve as reliable predictors for DR in early-stage type 2 diabetes. These findings contrast with prior cross-sectional studies suggesting a role for systemic low-grade inflammation in DR development. Inflammatory biomarkers. Diabetic retinopathy.

Aims: We investigated the association of the inflammatory biomarker YKL-40 with cardiovascular events (CVEs) and mortality in individuals with type 2 diabetes. Methods: We followed 11,346 individuals recently diagnosed with type 2 diabetes for up to 14 years. Baseline YKL-40 levels (measured in 9,010 individuals) were grouped into percentiles (0-33 %, 34-66 %, 67-90 %, and 91-100 %) and analyzed continuously (per 1 SD log increment), with comparisons to CRP (measured in 9,644 individuals). Cox regression assessed associations with atrial fibrillation (AF), ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), and all- cause, cardiovascular, and cancer mortality. Results: Adjusted HRs (95% CIs) for the highest (91-100%) versus the lowest (0-33%) YKL-40 percentile category were 1.31 (1.04-1.66) for AF, 1.43 (0.98-2.07) for IS, 1.07 (0.65-1.76) VTE, 0.88 (0.52-1.48) for MI, 1.66 (1.19-2.31) for HF, 1.66 (1.12-2.48) for PAD, and 2.18 (1.85-2.56) for all-cause, 1.64 (1.07-2.50) for cardiovascular, and 2.73 (2.05-3.63) for cancer mortality. Each 1 SD log increase in YKL-40 and CRP levels similarly increased CVE risks, with CRP being superior for MI and cardiovascular mortality. Conclusions: YKL-40 is a prognostic biomarker for most CVEs, and even more so for all-cause mortality, primarily driven by cancer-related causes.

OBJECTIVE:Unobserved automated office blood pressure (uAOBP) measurement is better correlated to daytime ambulatory blood pressure monitoring (dABPM) than traditional office blood pressure (BP) measurements. However, prolonged uAOBP duration may underestimate BP levels. We aimed to determine the duration of uAOBP that has the lowest proportion of white-coat hypertension (WCH) or masked hypertension (MH) compared with the gold-standard using dABPM in patients with type 2 diabetes (T2DM). Additionally, we examined variables associated with discrepancy between uAOBP and dABPM. METHODS:A total of 135 patients with T2DM underwent dABPM as well as uAOBP. uAOBP recordings were taken in the sitting position without prior rest for 24 min at 3-min intervals. Hypertension was defined as blood pressure ≥135/85 mmHg. Multiple uAOBP measurement intervals were compared with dABPM by the proportions of patients with WCH, MH, or consistent classification. RESULTS:Participants had a mean age of 57.7 years, 38% were female, and 66% used antihypertensive drugs. Average dABPM was 126.9/79.5 mmHg. Extension of uAOBP measurements from 3 to 24 min reduced the proportion with WCH significantly (20.7 vs. 27.4%, P  = 0.012), with an identical proportion of MH (4.4 vs. 3.7%). Higher BMI, higher urine albumin-creatinine ratio, and higher education were associated with MH, while WCH was associated with older age and early retirement. CONCLUSION:Extending the duration of uAOBP measurements from 3 to 24 min in patients with T2DM increased the proportion of patients with consistent classification by reducing WCH without increasing MH, but clinically relevant individual differences between uAOBP measurements and dABPM remained.

BACKGROUND:The admission systolic blood pressure (SBP) recorded at the emergency department is typically elevated and tends to decrease, while various degrees of blood pressure variability (BPV) remain. Whether admission SBP or mean SBP and BPV from resting beat-to-beat measurements are better associated with short-term outcome remains unknown. METHODS:We conducted a prospective study, including adults acutely admitted to the emergency department at a larger Danish tertiary care Hospital in Copenhagen, Denmark from 2019 to 2023. We measured blood pressure (BP) at admission and beat-to-beat BP and BPV during 10-minute rest. We defined BPV as the standard deviation from the mean of the beat-to-beat SBP measurements. Primary outcome was defined as 3-month all-cause mortality or readmission, and secondary outcome as 3-month cardiovascular mortality or readmission for cardiovascular disease. RESULTS:Among 951 patients included, mean age was 64 (standard deviation; 17) with 44% women. During 3-month follow-up, 284 (30%) patients met a primary outcome and 69 (7,2%) a secondary outcome. In adjusted Cox models, admission SBP, but neither mean SBP or BPV, was significantly associated with primary outcome [hazard ratio 0.971, 95% confidence interval (CI) 0.948-0.995, P  = 0.017] for each 5 mmHg increase in SBP. When exploring both extremes of upper and lower quartiles, BPV greater than 10 mmHg was associated with increased cardiovascular events (hazard ratio 2.019, 95% CI 1.142-3.569, P  = 0.016). CONCLUSION:In this study, low admission SBP was associated with all-cause readmissions and mortality, while BPV above 10 mmHg was associated with 3-month risk of cardiovascular events.

Catheter-based renal denervation of the sympathetic nerves (RDN) is still not a generally accepted treatment option for patients with resistant hypertension. Data on long-term outcomes, efficacy and safety beyond three years are scarce. We aimed to report the clinical outcomes after RDN in a cohort of 19 patients with resistant hypertension, followed for up to 11 years. We reviewed patient records from all consecutive patients who underwent RDN between January 2012 and October 2013. All recorded measurements of office blood pressure (BP) listed in the patient file, antihypertensive medications, cardiovascular events, and renal function between 2012 and 2023 were collected. For each year of follow-up (FU), the median office BP was calculated based on all available recordings. The primary endpoint was the change in systolic and diastolic office BP from baseline (prior RDN) to the final year of FU. A secondary endpoint was the change in office BP from baseline to the mean office BP across the entire FU period. A total of 19 consecutive patients underwent RDN treatment, 10 men and 9 women with a median age of 63 years (range 35–74 years). The median patient FU was nine years (interquartile range (IQR) 8–10 years). The median systolic BP decreased from 181 mmHg (IQR 28.5 mmHg) to 142 mmHg (IQR 23.5 mmHg), with a median reduction of 41 mmHg (IQR 25 mmHg) (p < 0.001). Similarly, the median diastolic BP decreased from 97 mmHg (IQR 13.5 mmHg) to 77 mmHg (IQR 8.5 mmHg), with a median reduction of 21 mmHg (IQR 9.5) (p < 0.001). The changes in BP showed large interindividual variation and the BP reduction appeared to be progressive over time. The antihypertensive medication 10 years after RDN did not differ significantly from the treatment given at baseline. The overall median reduction in total Daily Defined Dose (DDD) was -0.68 and not statistically significant (p = 0.45). In the present cohort of patients with resistant hypertension who underwent RDN 10 years previously, a sustained and progressive reduction in office BP was observed throughout the follow-up period, despite minimal changes in antihypertensive treatment.

BACKGROUND:Excessive consumption of glycyrrhizin (GL), a licorice-derived substance, can cause blood pressure (BP) elevation and apparent mineralocorticoid excess (AME). However, self-reported intake can be unreliable due to unrecognized sources of GL. Plasma levels of 18β-glycyrrhetinic acid (GA), a major metabolite of GL, may serve as a biochemical marker of exposure. Identifying individuals with high plasma levels of GA could be relevant in BP management in at-risk patients. OBJECTIVES:To examine whether plasma levels of GA are associated with BP, antihypertensive treatment intensity, resistant hypertension, and biochemical markers of AME in patients with type 2 diabetes (T2D). METHODS:In this cross-sectional study, we measured GA in plasma from 1160 patients with T2D. Participants were divided into high GA (top quartile) and low GA (bottom 3 quartiles). Linear and logistic regression models assessed associations of GA levels with BP, antihypertensive treatment intensity (defined daily dose; DDD), resistant hypertension and markers of AME. Models were adjusted for confounders such as age, sex, sociodemographic, lifestyle, diabetes duration, estimated glomerular filtration rate, glycated hemoglobin, homoeostasis model assessment 2 for insulin sensitivity, and where appropriate systolic BP and treatment. RESULTS:High GA was not significantly associated with higher BP but with more intensive antihypertensive treatment (+0.28 DDD [0.03-0.52], P = 0.03) compared with low GA. High GA was also associated with higher risk of resistant hypertension (adjusted odds ratio: 1.91 [1.12-3.24], P = 0.02). Additionally, high GA was associated with markers of AME (lower aldosterone (-41.5 pmol/L [-63.1 to -20.0]; P < 0.001), lower potassium (-0.06 mmol/L [-0.10 to -0.01]; P = 0.01), lower cortisone (-6.08 nmol/L [-7.78 to -4.38]; P < 0.001), and higher cortisol/cortisone ratio (+1.26 [1.00-1.52]; P < 0.001)). CONCLUSION:High GA levels, a possible marker of excessive licorice consumption, were associated with greater antihypertensive treatment intensity, resistant hypertension and biochemical markers consistent with AME in patients with T2D. These findings suggest that licorice-related exposure may be relevant to BP management in this population.

AIMS:Current guidelines recommend serial echocardiography at minimum 1-2-year intervals for monitoring patients with non-severe aortic valve stenosis (AS), which is costly and often clinically inconsequential. We aimed to develop and test whether the biomarker-based ASGARD (Aortic valve Stenosis Guarded by Amplified Risk Determination) risk score can guide the timing of echocardiograms in asymptomatic patients with non-severe AS. METHODS AND RESULTS:The development cohort comprised 1093 of 1589 (69%) asymptomatic patients with mild-to-moderate AS who remained event-free one year after inclusion into the SEAS trial. Cox regression landmark analyses with a 2-year follow-up identified the model (ASGARD) with the lowest Akaike information criterion for association to AS-related composite outcome (heart failure hospitalization, aortic valve replacement, or cardiovascular death). Fine-Gray analyses provided cumulative event rates by ASGARD score quartiles. The ASGARD score was internally validated in the remaining 496 patients (31%) from the SEAS cohort and externally in 71 asymptomatic outpatients with non-severe AS from six Copenhagen hospitals. The ASGARD score comprises updated measurements of heart rate and age- and sex-adjusted N-terminal pro-brain natriuretic peptide upon transaortic maximal velocity (Vmax) from the previous year. The ASGARD score had high predictive accuracy across all cohorts (external validation: area under the curve: 0.74 [95% CI, 0.62-0.86]), and similar to an updated Vmax measurement. An ASGARD score ≤ 50% was associated with AS-related event rates ≤ 5% for a minimum of 15 months. CONCLUSION:The ASGARD score could provide a personalized and safe surveillance alternative to routinely planned echocardiograms, so physicians can prioritize echocardiograms for high-risk patients.

Strenuous physical activity alleviates the risk of elevated blood pressure (BP) presumably through a reduction in systemic vascular resistance (SVR). Using logistic multivariate regression models, we investigated whether moderate to vigorous physical activity (MVPA) was negatively associated with high SVR among adults with Type 2 Diabetes (T2DM). Additionally, we assessed associations between other cardiometabolic risk factors and SVR. SVR was assessed using thoracic electrical bioimpedance; high SVR was defined as ≥20

BACKGROUND:The evidence supporting beta-blocker therapy after myocardial infarction was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies. METHODS:In an open-label, randomized trial with blinded end-point evaluation, conducted in Denmark and Norway, we assigned patients who had had a myocardial infarction and who had a left ventricular ejection fraction of at least 40%, in a 1:1 ratio, to receive long-term beta-blocker therapy within 14 days after the event or no beta-blocker therapy. The primary end point was a composite of death from any cause or major adverse cardiovascular events (new myocardial infarction, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias). RESULTS:A total of 5574 patients underwent randomization and were included in the main analyses - 2783 in the beta-blocker group and 2791 in the no-beta-blocker group. After a median follow-up of 3.5 years (interquartile range, 2.2 to 4.6), a primary end-point event had occurred in 394 patients (14.2%) in the beta-blocker group and in 454 patients (16.3%) in the no-beta-blocker group (hazard ratio, 0.85; 95% confidence interval [CI], 0.75 to 0.98; P = 0.03). Death from any cause occurred in 4.2% of the patients in the beta-blocker group and in 4.4% of those in the no-beta-blocker group; myocardial infarction occurred in 5.0% and 6.7%, respectively (hazard ratio, 0.73; 95% CI, 0.59 to 0.92), unplanned coronary revascularization in 3.9% and 3.9%, ischemic stroke in 1.6% and 1.3%, heart failure in 1.5% and 1.9%, and malignant ventricular arrhythmias in 0.5% and 0.6%. No apparent differences in safety outcomes were observed between the groups. CONCLUSIONS:Among patients with a myocardial infarction and a left ventricular ejection fraction of at least 40%, beta-blocker therapy led to a lower risk of death or major adverse cardiovascular events than no beta-blocker therapy. (Funded by the Health South-East research program in Norway and others; BETAMI-DANBLOCK ClinicalTrials.gov numbers, NCT03646357 and NCT03778554.).

We examined the association of serum YKL-40, an inflammatory biomarker, with incident cancer risk in early type 2 diabetes. A cohort of 11,346 individuals newly diagnosed with type 2 diabetes was followed for up to 14 years. YKL-40 levels (n = 9010) were categorised into five percentiles (0–33%, 34–66%, 67–90%, 91–95%, and 96–100%), and baseline YKL-40 and CRP (n = 9644) were analyzed continuously (per 1 SD log increment) for comparison. Cox regression models assessed associations with obesity-related, gastrointestinal, liver, pancreatic, colorectal, bladder and lung cancers, as well as cancers of reproductive organs. Adjusted HRs (95% CIs) for the highest versus lowest YKL-40 category were 2.4 (1.6–3.7) for obesity-related, 2.6 (1.7–4.1) for gastrointestinal, 44.2 (12.8–153.4) for liver, and 4.2 (1.3–14.1) for bladder cancers. No associations were found for other cancers. YKL-40 and CRP had similar prognostic abilities for obesity-related and gastrointestinal cancers, but YKL-40 outperformed CRP for liver and bladder cancers. Conversely, CRP was a stronger predictor for lung, colorectal, and ovarian cancers. YKL-40 was associated with the risks of liver and bladder cancers, clearly outperforming CRP for these cancers. This suggests distinct prognostic roles for YKL-40 and CRP, and highlights YKL-40 as a promising biomarker for liver cancer.

The incidence of certain disease events such as myocardial infarction, stroke, aortic rupture, and sudden cardiac death is affected by the time of day. It is thus theorized that synchronization of medication timing with circadian rhythmicity (or at the minimum, clock time) may improve treatment efficacy and/or reduce the risk of serious adverse events. We launched the C 3 (Cardiovascular Circadian Chronotherapy) trial concept to efficiently conduct randomized, controlled, clinical outcome trials of the timing of medication administration. This concept takes advantage of the Danish nationwide administrative health registries for participant identification and collection of baseline and follow-up data as well as the mandatory governmental electronic letter system. Although many of these interventions may only provide small effect sizes, any positive effects from simple changes in the timing of drug administration could potentially lead to large, worldwide prognostic improvements. (JACC Adv. 2025;4:102147) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:Heart failure (HF) is an increasing health problem globally. Profound sex-related differences have been observed regarding the cause, treatment, and prognosis of HF. AIM:To assess baseline predictors for achieving optimal medical treatment (OMT) and the prognostic importance of OMT for male and female patients who have attended a HF clinical program (HFCP). METHODS:OPTIHEART was a retrospective study that included 870 consecutive patients with left ventricular ejection fraction (LVEF)≤40% discharged from HFCP in 2018, 2019 or 2020 and followed in registers for a mean of 1083(SD 11.3) days. OMT was defined as receiving an angiotensin-converting-enzyme-inhibitor (ACEi), angiotensin-receptor blocker (ARB) or angiotensin-II-receptor blocker and nephrylisin-inhibitor (ARNI) AND a betablocker (BB) both in doses ≥ 50% of target doses. RESULTS:Achieving OMT was associated with male sex (OR: 2.05 95%CI 1.44-2.97; p < 0.0001) independently of younger age, higher diastolic blood pressure (DBP), and lower creatinine. A lower rate of 5-point MACE was associated with achieved OMT (HR: 0.67 95%CI 0.50-0.90; p = 0.007) independently of female sex (HR: 0.64 95%CI 0.48-0.84; p = 0.002), younger age, never smoking and NYHA ≤ 2. The beneficial effect of OMT was insignificantly more pronounced in patients with male sex, older age, higher creatinine, lower DBP, and body mass index ≤25kg/m2. CONCLUSION:OMT was more frequently achieved in patients with male sex independently of age, DBP, and creatinine. Achieving OMT was associated with less 5-point MACE independently of female sex, younger age, never smoking and NYHA ≤ 2.

INTRODUCTION:Cardiovascular disease (CVD) risk remains high but unevenly distributed in patients with type 2 diabetes mellitus (T2DM). Current risk stratification strategies are far from optimal, leading to both undertreatment and overtreatment of patients. The STENO INTEN-CT trial aims to evaluate a strategy of improved CVD risk management by using cardiac CT (coronary artery calcification (CAC)) for stratification and tailoring of multifactorial cardiovascular treatment based on CAC score. We hypothesise that (1) intensified medical treatment will lower CVD event rates in high-risk patients (CAC≥100), and (2) less intensive multifactorial treatment is safe in very low-risk patients (CAC=0). METHODS AND ANALYSIS:The Steno INTEN-CT trial is an investigator-initiated, pragmatic, open-label, event-driven randomised controlled trial including patients with T2DM without known CVD. All participants (expected n=7300) will be invited for a non-contrast coronary CT scan. After the scan, participants will be randomised to either standard treatment (blinded for CAC results) or CAC-based treatment. Participants in CAC-based treatment and their general practitioner (GP) will receive information on CAC and a recommendation of multifactorial treatment. High-risk participants in the interventional arm will be invited for one or more initial study visits to intensify treatment with a combination of sodium glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, high-dose lipid-lowering, antihypertensive and antithrombotic treatment. Very low-risk patients in the interventional arm will be recommended less intensive treatment targets. After initial study-related activities, all participants will continue to be taken care of by their GP guided by specific treatment recommendations. The primary outcome in the primary hierarchical analysis (the rate of the combined CVD endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for heart failure) will be monitored through national health registries. The trial is event-driven, but a median follow-up of 5 years is expected. Key secondary outcomes include patient-reported outcomes, quality-adjusted life years and healthcare costs. ETHICS AND DISSEMINATION:The protocol V.1.9 is approved by the Research Ethics Committee and the Danish Medicines Agency and the Danish Data Protection Agency. The results of the study-positive, negative or neutral-will be published in peer-reviewed journals and through www. CLINICALTRIALS:org. TRIAL REGISTRATION NUMBER:NCT05700877.

Background: Despite significant advancements in diabetes care, many individuals with type 2 diabetes (T2D) do not receive optimal care and treatment. Digital interventions promoting behavioral changes have shown promising long-term results in supporting healthier lifestyles but are not implemented in most healthcare offerings, maybe due to lack of general practice support and collaboration. This study evaluates the efficacy of the Digital, Individualized, and Collaborative Treatment of T2D in General Practice Based on Decision Aid (DICTA), a randomized controlled trial integrating a patient-centered smartphone application for lifestyle support in conjunction with a clinical decision support (CDS) tool to assist general practitioners (GPs) in optimizing antidiabetic treatment. Methods: The present randomized controlled trial aims to recruit 400 individuals with T2D from approximately 70 GP clinics (GPCs) in Denmark. The GPCs will be cluster-randomized in a 2:3 ratio to intervention or control groups. The intervention group will receive one year of individualized eHealth lifestyle coaching via a smartphone application, guided by patient-reported outcomes (PROs). Alongside this, the GPCs will have access to the CDS tool to optimize pharmacological decision-making through electronic health records. The control group will receive usual care for one year, followed by the same intervention in the second year. Results: The primary outcome is the one-year change in estimated ten-year cardiovascular risk, assessed by SCORE2-Diabetes calculated from age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, age at diabetes diagnosis, HbA1c, and eGFR. Conclusions: If effective, DICTA could offer a scalable, digital-first approach for improving T2D management in primary care by combining patient-centered lifestyle coaching with real-time pharmacological clinical decision support.