Objective—: The renin–angiotensin system is thought to play a pivotal role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on human AAAs remain unclear. We therefore examined whether treatment with ACEIs or ARBs influenced hard clinical end points in a nation-wide cohort of patients with AAA. Approach and Results—: All patients diagnosed with AAA during the period 1995 to 2011 were identified from the Danish nation-wide registries. Subjects were divided according to ACEI and ARB treatment status and followed up for an average of 5 years. Study outcomes were evaluated by time-dependent Cox proportional hazard models. Of 9441 patients with AAA, 12.6% were treated with ACEIs and 5.0% received ARBs. Incidence rates of death from AAA per 100 patient-years were 3.7, 3.6, 4.0, and 4.7 for treatment with ACEIs or ARBs, ACEIs, ARBs, and no ACEI/ARB, respectively. Hazard ratios of death from AAA were 0.64 (95% confidence interval, 0.51–0.80; P <0.001) for patients receiving ACEIs and 0.65 (95% confidence interval, 0.48–0.88; P =0.006) for those receiving ARBs, respectively ( P for difference=0.944). The risk of surgery for AAA was significantly reduced in patients receiving ACEIs (hazard ratio, 0.86 [95% confidence interval, 0.74–0.99]; P =0.040) but not in patients receiving ARBs (hazard ratio, 1.02 [95% confidence interval, 0.84–1.23]; P =0.867; P for difference=0.119). Conclusions—: In this observational study, treatment with ACEIs or ARBs was associated with a comparable reduction in mortality but not in surgery for AAA among patients with AAA. Randomized controlled trials are warranted to confirm these findings.

Objective: To examine whether patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV. Methods: Using a nested case–control framework, patients with granulomatosis with polyangiitis and microscopic polyangiitis were identified through the Danish Nationwide Registries from 1996 to 2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted hazard ratios (HRs) for major adverse cardiovascular events (MACE), ischaemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischaemic stroke, pericarditis and ventricular arrhythmias/implantable cardioverter defibrillator implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date. Results: A total of 2371 patients with AAV (median age 63 years, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared with 3.8% [HR 3.05 (95% CI 2.48–3.75)] and 1.3% [HR 1.98 (95% CI 1.39–2.82)] of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: any cardiovascular outcome [HR 10.73 (95% CI 7.05–16.32)] and MACE [HR 5.78 (95% CI 2.67–12.52)]. In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA). Conclusions: AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance towards cardiovascular disease.

Objectives: To examine long-term cardiovascular outcomes and temporal trends among patients with ANCA-associated vasculitis (AAV) using Danish nationwide registries. Methods: Using a cohort design, we examined patients with granulomatosis with polyangiitis (ICD-10: DM31.3) and microscopic polyangiitis (ICD-10: DM3.17) in Denmark from 1996–2018. Hazard ratios (HRs) of cardiovascular outcomes were compared between patients with AAV and age and gender-matched controls. Counterfactual G-estimation of HRs was performed to estimate 5-year absolute risks. Temporal trends were obtained by grouping cohorts into evenly distributed tertiles according to inclusion year. Results: A total of 2306 patients with AAV (median age: 62.9yrs, 52.6% male) were matched with 6918 controls. Median follow-up was 9.5yrs. Patients with AAV had a higher rate of ischaemic heart disease [HR 1.86 (1.62–2.15)], myocardial infarction [HR 1.62 (1.26–2.09)], coronary angiogram [HR 1.64 (1.37–1.96)], percutaneous coronary intervention [HR 1.56 (1.17–2.07)] and ventricular arrhythmias/implantable-cardioverter-defibrillator (ICD)-implantations [HR 2.04 (1.16–3.57)]. Similarly, an increased rate of heart failure [HR 2.12 (1.77–2.54)], deep vein thrombosis [HR 3.13 (2.43–4.05)], pulmonary embolism [HR 4.04 (3.07–5.32)], atrial fibrillation [HR 2.08 (1.82–2.39)], ischaemic stroke [HR 1.58 (1.31–1.90)] and in-hospital cardiac arrest [HR 2.27 (1.49–3.48)] was observed. The 5-year risk of all outcomes were significantly higher (excluding ventricular arrhythmia/ICD-implantations). For temporal trends among patients with AAV, a decreased 3-year risk of cardiovascular mortality was observed over time. Conclusions: Patients with AAV are at increased risk of heart failure, atrial-/ventricular arrhythmias, venous thrombotic events, ischaemic stroke and myocardial infarction. Furthermore, patients with AAV were more frequently examined with coronary procedures and underwent more coronary revascularizations. No temporal changes in ischaemic cardiovascular outcomes were observed, albeit the cardiovascular mortality has decreased over time.

The mortality following blood stream infection (BSI) and risk of subsequent BSI in relation to dialysis modality, vascular access, and other potential risk factors has received relatively little attention. Consequently, we assessed these matters in a retrospective cohort study, by use of the Danish nation-wide registries. Patients more than 17 years of age, who initiated dialysis between 1.1.2010 and 1.1.2014, were grouped according to their dialysis modality and vascular access. Survival was modeled in time-dependent Cox proportional hazard analyses. Potential risk factors confined by a modified Charlson comorbidity index (MCCI), were subsequently assessed in stepwise selection models. At baseline, 764 patients received peritoneal dialysis (PD), and 434, 479, and 782 hemodialysis (HD) patients were dialyzed by use of arteriovenous fistulas (AVFs), tunneled catheters (TCs), and non-tunneled catheters (NTCs), respectively. We identified 1069 BSIs with an overall incidence rate of 17.7 episodes per 100 person years, and 216 BSIs occurred more than one time in the same patient. HRs of post BSI mortality relative to PD were 3.20 (95% CI 1.86–5.50; p < 0.001) with NTCs; whereas no associations were found for AVF and TC. The risk of subsequent BSIs was higher with NTCs [HR 2.29 (95% CI 1.09–4.82), p = 0.030], and no significant difference was found for AVF and TC, in relation to PD. There was an increased risk of both outcomes with TC relative to AVF [death: 1.57 (95% CI 1.07–2.29, P < 0.021); BSI: 1.78 (95% CI 1.13–2.83, P < 0.014], and risk of death was reduced in patients who changed to AVF after first-time BSI. The MCCI was significantly associated with the risk of subsequent BSI and post BSI death; however, only some of the variables contained in the index were found to be significant risk predictors when analyzed in the fitted model. While NTC was the most predominant risk factor for subsequent BSI and post BSI mortality, AVF appeared protective.

Evidence for pharmacogenetic risk stratification of angiotensin-converting enzyme inhibitor (ACEI) treatment is limited. Therefore, in a cohort of ACEI-treated patients with congestive heart failure (CHF), we investigated the predictive value of two pharmacogenetic scores that previously were found to predict ACEI efficacy in patients with ischemic heart disease and hypertension, respectively. Score A combined single nucleotide polymorphisms (SNPs) of the angiotensin II receptor type 1 gene (rs275651 and rs5182) and the bradykinin receptor B1 gene (rs12050217). Score B combined SNPs of the angiotensin-converting enzyme gene (rs4343) and ABO blood group genes (rs495828 and rs8176746). Danish patients with CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were included. Subjects were genotyped and categorized according to pharmacogenetic scores A and B of ≤1, 2 and ≥3 each, and followed for up to 10 years. Difference in cumulative incidences of cardiovascular death and all-cause death were assessed by the cumulative incidence estimator. Survival was modeled by Cox proportional hazard analyses. We included 667 patients, of whom 80% were treated with ACEIs. Differences in cumulative incidences of cardiovascular death (P = 0.346 and P = 0.486) and all-cause death (P = 0.515 and P = 0.486) were not significant for score A and B, respectively. There was no difference in risk of cardiovascular death or all-cause death between subjects with score A ≤1 vs. 2 (HR 1.03 [95% CI 0.79–1.34] and HR 1.11 [95% CI 0.88–1.42]), score A ≤1 vs. ≥3 (HR 0.80 [95% CI 0.59–1.08] and HR 0.91 [95% CI 0.70–1.20]), score B ≤1 vs. 2 (HR 1.02 [95% CI 0.78–1.32] and HR 0.98 [95% CI 0.77–1.24]), and score B ≤1 vs. ≥3 (HR 1.03 [95% CI 0.75–1.41] and HR 1.05 [95% CI 0.79–1.40]), respectively. We found no association between either of the analyzed pharmacogenetic scores and fatal outcomes in ACEI-treated patients with CHF.