The significant increase in the average life expectancy has increased the societal challenge of managing serious age-related diseases, especially cancer and cardiovascular diseases. A routine check by a general practitioner is not sufficient to detect incipient cardiovascular disease. Population-based randomized clinically controlled screening trial. Participants: 45,000 Danish men aged 65–74 years living on the Island of Funen, or in the surrounding communities of Vejle and Silkeborg. No exclusion criteria are used. Interventions: One-third will be invited to cardiovascular seven-faceted screening examinations at one of four locations. The screening will include: (1) low-dose non-contrast CT scan to detect coronary artery calcification and aortic/iliac aneurysms, (2) brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension, (3) a telemetric assessment of the heart rhythm, and (4) a measurement of the cholesterol and plasma glucose levels. Up-to-date cardiovascular preventive treatment is recommended in case of positive findings. Objective: To investigate whether advanced cardiovascular screening will prevent death and cardiovascular events, and whether the possible health benefits are cost effective. Outcome: Registry-based follow-up on all cause death (primary outcome), and costs after 3, 5 and 10 years (secondary outcome). Randomization: Each of the 45,000 individuals is, by EPIDATA, given a random number from 1–100. Those numbered 67+ will be offered screening; the others will act as a control group. Blinding: Only those randomized to the screening will be invited to the examination;the remaining participants will not. Numbers randomized: A total of 45,000 men will be randomized 1:2. Recruitment: Enrollment started October 2014. Outcome: A 5 % reduction in overall mortality (HR = 0.95), with the risk for a type 1 error = 5 % and the risk for a type II error = 80 %, is expected. We expect a 2-year enrollment, a 10-year follow-up, and a median survival of 15 years among the controls. The attendance to screening is assumed to be 70 %. The primary aim of this so far stand-alone population-based, randomized trial will be to evaluate the health benefits and costeffectiveness of using non-contrast full truncus computer tomography (CT) scans (to measure coronary artery calcification (CAC) and identify aortic/iliac aneurysms) and measurements of the ankle brachial blood pressure index (ABI) as part of a multifocal screening and intervention program for CVD in men aged 65–74. Attendance rate and compliance to initiated preventive actions must be expected to become of major importance. Current Controlled Trials: ISRCTN12157806 (21 March 2015).

To examine the temporal trends and factors associated with national cardiac rehabilitation (CR) referral and compare the risk of hospital readmission and mortality in those referred for CR versus no referral. This cohort study includes all adult patients alive 120 days from incident heart failure (HF) identified by the Danish Heart Failure Registry (n = 33 257) between 2010 and 2018. Multivariable logistic regression models were used to assess the association between CR referral and patient factors and acute all-cause hospital readmission and mortality at 1 year following HF admission. Overall, 46.7% of HF patients were referred to CR, increasing from 31.7% in 2010 to 52.2% in 2018. Several factors were associated with lower odds of CR referral: male sex [odds ratio (OR): 0.85; 95% confidence interval: 0.80–0.89], older age, unemployment, retirement, living alone, non-Danish ethnic origin, low educational level, New York Heart Association (NYHA) class IV vs. I (OR: 0.75; 0.60–0.95), left ventricular ejection fraction >40%, and comorbidity (stroke, chronic kidney disease, atrial fibrillation/flutter, and diabetes). Myocardial infarction, arthritis, coronary artery bypass grafting, percutaneous coronary intervention, valvular surgery, NYHA class II, and use of angiotensin-converting enzyme inhibitors were associated with higher odds of CR referral. CR referral was associated with lower risk of acute all-cause readmission (OR: 0.92; 0.87–0.97) and all-cause mortality (OR: 0.65; 0.58–0.72). Although increased over time, only one in two HF patients in Denmark were referred to CR in 2018. Strategies are needed to reduce referral disparities, focusing on subgroups of patients at highest risk of non-referral. Factors associated with referral to cardiac rehabilitation.

Background: Patients with aortic stenosis ( AS ) often have concomitant hypertension. Antihypertensive treatment with a β‐blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS . Methods and Results: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity‐matched Cox regression and competing risk analyses were used to assess risk ratios for all‐cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow‐up of 4.3±0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all‐cause mortality (hazard ratio 0.5, 95% confidence interval 0.3‐0.7, P <0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2‐0.7, P <0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1‐0.6, P =0.004). This was confirmed in competing risk analyses (all P <0.004). No interaction was detected with AS severity (all P >0.1). Conclusions: In post hoc analyses Bbl therapy did not increase the risk of all‐cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS . A prospective study may be warranted to determine if Bbl therapy is in fact beneficial. Clinical Trial Registration: URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00092677.

Background and Purpose—: There are limited data on risk stratification of stroke in aortic stenosis. This study examined predictors of stroke in aortic stenosis, the prognostic implications of stroke, and how aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting influenced the predicted outcomes. Methods—: Patients with mild-to-moderate aortic stenosis enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were exclusion criteria. Ischemic stroke was the primary end point, and poststroke survival a secondary outcome. Cox models treating AVR as a time-varying covariate were adjusted for atrial fibrillation and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years and female sex (CHA ₂ DS ₂ -VASc) scores. Results—: One thousand five hundred nine patients were followed for 4.3±0.8 years (6529 patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre- and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1–6.6), CHA ₂ DS ₂ -VASc score (HR 1.4 per unit; 95% CI, 1.1–1.8), diastolic blood pressure (HR, 1.4 per 10 mm Hg; 95% CI, 1.1–1.8), and AVR with concomitant coronary artery bypass grafting (HR, 3.2; 95% CI, 1.4–7.2, all P ≤0.026) were independently associated with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7–14.0; P <0.001). Conclusions—: In patients with aortic stenosis not prescribed oral anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass grafting, and CHA ₂ DS ₂ -VASc score were the major predictors of stroke. Incident stroke was strongly associated with mortality. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00092677.

BACKGROUND: Abdominal aortic aneurysms (AAA) present with high morbidity and mortality when they occasionally rupture. No medical therapy has successfully been proven to reduce AAA growth, though both metformin and statins have been identified as potential treatments in multiple meta-analysis. This study aimed to investigate a potential relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death. METHODS: The study population included all men with screening-detected AAAs (30–55 mm) from the 2 large, population-based, randomized screening trials; the Viborg Vascular Screening trial (inclusion, 2008–2011) and the Danish Cardiovascular Screening trial (inclusion, 2014–2018). The clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. Statin exposure was quantified by defined daily doses (DDD). The primary outcome was AAA growth rate, whereas secondary outcomes included the need for repair and a composite of repair, rupture, and all-cause death. Growth rates were calculated using linear regression. To evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, 5-year follow-up, or December 31, 2021. RESULTS: A total of 998 aneurysmal men (median age, 69.5 [interquartile range (IQR), 67–72] years; median AAA diameter, 35.4 [IQR, 32–41.2] mm) were included. Statin use was significantly associated with reduced AAA growth rate; an increase of 1 DDD statin per day was associated with an adjusted change in growth rate of −0.22 mm/year [95% CI, −0.39 to −0.06]; P =0.009). The 5-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a significantly reduced adjusted hazard ratio (HR) of 0.82 ([95% CI, 0.70–0.97]; P= 0.023), which was significant after 2.5 years. Statin use was associated with a significantly lower risk of the composite outcome (surgery, rupture, and death) in a dose-dependent manner, with an adjusted HR of 0.83 ([95% CI, 0.73–0.94]; P =0.003) per doubling of statin dose. Findings were robust in a variety of sensitivity analyses. CONCLUSIONS: High-dose statin use was associated with decreased AAA growth rates and lowered risk of undergoing repair, rupture, and death. This nonrandomized study suggests that patients with AAA could benefit from high-dose statin use, beyond only targeting associated risk factors.

Background: Pericoronary adipose tissue attenuation (PCATa), derived from coronary computed tomography angiography (CCTA), is a novel marker of inflammation in the coronary arteries. Patients with type 2 diabetes mellitus (T2DM) are at elevated risk of coronary artery disease (CAD), potentially due to systemic inflammation. This study evaluated whether baseline PCATa predicts changes in plaque composition and burden over 12 months. Methods: This prospective longitudinal study included 200 participants with T2DM, who had neither symptoms nor a prior diagnosis of CAD (mean age 61 ± 9.4 years, 72% male). PCATa was measured at the baseline scan along the proximal 40 mm of each major coronary artery, and the values were averaged to calculate the participant-level PCATa. High PCATa levels were determined using the validated cut-off of -70.1 Hounsfield units. Compositional plaque changes were quantified as the differences between baseline and 12-month scans, and plaque burden was calculated as the normalized atheroma volume. Multivariable regression analyses assessed the associations between baseline PCATa and compositional plaque changes and evaluated risk factors, including high PCATa, in predicting non-calcified plaque burden progression. Results: Plaque compositional volumes and burden increased over 12 months, while PCATa remained stable. After multivariable adjustments, baseline PCATa was significantly associated with changes in total plaque volume (β = 0.005, p = 0.005), non-calcified plaque volume (β = 0.006, p = 0.007), total plaque burden (β = 1.7, p = 0.007), and non-calcified plaque burden (β = 2.0, p = 0.006), but not with calcified plaque volume or burden. High baseline PCATa was observed in 44 participants (22%) and was the only independent predictor of non-calcified plaque burden progression (odds ratio 3.5, p = 0.002). Conclusions: Baseline PCATa is significantly associated with increases in total and non-calcified plaque volumes and burden over 12 months in participants with T2DM without symptoms or known CAD. High PCATa levels uniquely predict non-calcified plaque burden progression, suggesting that PCATa may serve as a marker for subclinical atherosclerosis progression. This warrants further investigation into PCATa for cardiovascular risk assessment, particularly in high-risk populations such as individuals with T2DM. Trial registration: Trial registration: NCT06644651. Graphical PCATa = Pericoronary Adipose Tissue attenuation. T2DM = Type 2 diabetes mellitus. CAD = Coronary Artery Disease. N = numbers. CCTA = Coronary CT angiography. Created in BioRender. Research insights: What is currently known about this topic? Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) share inflammatory mechanisms. Individuals with T2DM face a two- to four-fold increased risk of CAD compared with those without T2DM. Pericoronary adipose tissue attenuation (PCATa) is a novel marker of coronary inflammation. What is the key research question? Can baseline PCATa predict compositional plaque changes over 12 months in T2DM without known CAD? What is new? Baseline PCATa relates to higher total and non-calcified plaque (NCP) volumes after adjustment. Baseline PCATa associates with increased total- and NCP burden after multivariable adjustment. High baseline PCATa (> -70.1 HU) independently predicts NCP burden progression. How might this study influence clinical practice? PCATa may be a marker for subclinical atherosclerosis progression.