Sleep apnea, the risk of out-of-hospital cardiac arrest, and potential benefits of continuous positive airway pressure therapy: A nationwide study.

OBJECTIVE: Patients with sleep apnea (SA) are at increased cardiovascular risk. However, little is known about the risk of out-of-hospital cardiac arrest (OHCA) in patients with SA. Therefore, we studied the relation between SA patients who did and did not receive continuous positive airway pressure (CPAP) therapy with OHCA in the general population. METHODS: Using nationwide databases, we conducted a nested case-control study with OHCA-cases of presumed cardiac causes and age/sex/OHCA-date matched non-OHCA-controls from the general population. Conditional logistic regression models with adjustments for well-known OHCA risk factors were performed to generate odds ratio (OR) of OHCA comparing patients with SA receiving and not receiving CPAP therapy with individuals without SA. RESULTS: We identified 46,578 OHCA-cases and 232,890 matched non-OHCA-controls [mean: 71 years, 68.8% men]. Compared to subjects without SA, having SA without CPAP therapy was associated with increased odds of OHCA after controlling for relevant confounders (OR:1.20, 95%-Cl:1.06-1.36), while having SA with CPAP therapy was not associated with OHCA (OR:1.04, 95%-Cl:0.93-1.36). Regardless of CPAP therapy, age and sex did not significantly influence our findings. Our findings were confirmed in: (I) patients with neither ischemic heart disease nor heart failure (untreated SA, OR:1.24, 95%-CI:1.04-1.47; SA with CPAP, OR:1.08, 95%-CI:0.93-1.25); and (II) in patients without cardiovascular disease (untreated SA, OR:1.33, 95%-CI:1.07-1.65; SA with CPAP, OR:1.14, 95%-CI:0.94-1.39). CONCLUSION: SA not treated with CPAP was associated with OHCA, while no increased risk of OHCA was found for SA patients treated with CPAP.

Fluoroquinolones do not provide added risk of out-of-hospital cardiac arrest: a nationwide study.

AIM: Conflicting results have been reported regarding the association between fluoroquinolones (FQs) and the risk of out-of-hospital cardiac arrest (OHCA). In particular, it has not become clear whether OHCA in FQ users is related to the inherent comorbidities or whether there is a direct pro-arrhythmic effect of FQs. Therefore, we studied the relation between FQs and OHCA in the general population. METHODS: Through Danish nationwide registries, we conducted a nested case-control study with OHCA cases of presumed cardiac causes and age/sex/OHCA date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the OR with 95% CI of OHCA comparing FQs with amoxicillin. RESULTS: The study population consisted of 46 578 OHCA cases (mean: 71 years (SD: 14.40), 68.8% men) and 232 890 matched controls. FQ was used by 276 cases and 328 controls and conferred no increase in the odds of OHCA compared with amoxicillin use after controlling for the relevant confounders (OR: 0.91 (95% CI: 0.71 to 1.16)). The OR of OHCA associated with FQ use did not vary significantly by age (OR≤65: 0.96 (95% CI: 0.53 to 1.74), OR>65: 0.88 (95% CI: 0.67 to 1.16), p value interaction=0.7818), sex (ORmen: 0.96 (95% CI: 0.70 to 1.31), ORwomen: 0.80 (95% CI: 0.53 to 1.20), p value interaction=0.9698) and pre-existing cardiovascular disease (ORabsent: 1.02 (95% CI: 0.57 to 1.82), ORpresent: 0.98 (95% CI: 0.75 to 1.28), p value interaction=0.3884), including heart failure (ORabsent: 0.93 (95% CI: 0.72 to 1.22), ORpresent: 1.11 (95% CI: 0.61 to 2.02), p value interaction=0.7083) and ischaemic heart disease (ORabsent: 0.85 (95% CI: 0.64 to 1.12), ORpresent: 1.38 (95% CI: 0.86 to 2.21), p value interaction=0.6230). CONCLUSION: Our findings do not support an association between FQ exposure and OHCA in the general population. This lack of association was consistent in men and women, in all age categories, and in the presence or absence of cardiovascular disease.

Discontinuation and reinitiation of SGLT-2 inhibitors and GLP-1R agonists in patients with type 2 diabetes: a nationwide study from 2013 to 2021.

Background: Small observational studies have observed poor persistency to sodium-glucose cotransporter-2 inhibitors (SGLT2-i) and glucacon-like-peptide-1-receptor agonists (GLP1-RA), contrary to what has been reported in clinical trials. Therefore, we investigated the risk of discontinuing SGLT2-is and GLP1-RAs in patients with type 2 diabetes (T2D) in a nationwide population. Methods: From Danish nationwide registers, all first-time users of SGLT2-is and GLP1-RAs from 2013 to 2021 were identified. Adherence over the first year of therapy, the five-year risk of discontinuing therapy for the first time and the subsequent one-year probability of reinitiating therapy, was assessed. The Aalen-Johansen estimator was used to account for censoring and competing risks and multivariable Cox regression models were used to identify covariates associated with discontinuation. Findings: A total of 77,745 first-time users of SGLT2-is (64% male, median age 64 [interquartile range 56-72]) and 56,037 first-time users of GLP1-RAs (56% male, median age 61 [53-70]) were included. The absolute five-year risk of discontinuing therapy was 56% (95% CI: 55-57) and 45% (45-46) for SGLT2-i- and GLP1-RA users, respectively, with a significantly decreased risk over the period studied. The subsequent one-year probability of reinitiating therapy was 24% (95% CI: 24-25) for initial SGLT2-i users and 26% (25-27) for GLP1-RA users. Interpretation: Approximately half of the users of SGLT2-is and GLP1-RAs discontinued therapy within five years, respectively. However, a large proportion of these patients reinitiated therapy during the following year. Further insight into the reasons for discontinuation and initiatives to reduce the time to reinitiation in eligible patients are warranted. Funding: The work was funded by an unrestricted research grant from 'Department of Cardiology, Herlev and Gentofte University Hospital'.

Long-term stress conditions and out-of-hospital cardiac arrest risk: a nested case-control study.

OBJECTIVE: Patients with stress-related disorders and anxiety are at increased risk of developing cardiovascular disease. However, the risk of out-of-hospital cardiac arrest (OHCA) is scarcely investigated. We aimed to establish whether long-term stress (post-traumatic stress disorder, adjustment disorder) or anxiety is associated with OHCA in the general population. METHODS: We conducted a nested case-control study in a nationwide cohort of individuals between 1 June 2001 and 31 December 2015 in Denmark. Cases were OHCA patients with presumed cardiac causes. Each case was matched by age, sex and date of OHCA with 10 non-OHCA controls from the general population. HRs for OHCA were derived from Cox models after controlling for common OHCA risk factors. Stratified analyses were performed according to sex, age and pre-existing cardiovascular disease. RESULTS: We included 35 195 OHCAs and 351 950 matched controls (median age 72 years; 66.8% male). Long-term stress conditions were diagnosed in 324 (0.92%) OHCA cases and 1577 (0.45%) non-OHCA controls, and were associated with higher rate of OHCA (HR 1.44, 95% CI 1.27 to 1.64). Anxiety was diagnosed in 299 (0.85%) OHCA cases and 1298 (0.37%) controls, and was associated with increased rate of OHCA (HR 1.56, 95% CI1.37 to 1.79). We found no interaction with sex, age or history of cardiovascular diseases. CONCLUSION: Patients with stress-related disorders or anxiety have an increased rate of OHCA. This association applies equally to men and women and is independent from the presence of cardiovascular disease. Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients.

Association between early detected heart failure stages and future cardiovascular and non-cardiovascular events in the elderly (Copenhagen Heart Failure Risk Study).

BACKGROUND: Early stages of heart failure (HF) are associated with an increased risk of hospitalization and increased mortality, however the course of progression and the impact of non-cardiovascular comorbidities on adverse events in elderly high-risk patients are unknown. AIM: To examine the risk of future cardiovascular (CV) and non-CV events in early stages of HF in a cohort of elderly patients (age ≥ 60 with ≥ 1 risk factor for HF and without known or clinically suspected HF). METHODS: A total of 400 patients (American Heart Association HF stage A: N = 177; stage B: N = 150; stage C: N = 73) from the Copenhagen Heart Failure Risk Study were identified and followed for the main composite outcome of a HF hospitalization (HFH), ischemic heart disease (IHD), stroke, and all-cause death, recorded within the Danish nationwide registries. Non-CV hospitalization was a secondary outcome. Absolute risk was calculated by the Aalen-Johansen estimator. RESULTS: The median follow-up time was 3.3 years, total number of events were 83, and the 3-year risk (95% confidence interval) of the main outcome was 12.8% (7.8-17.9), 22.8% (16.1-29.6) and 31.8% (21.0-42.6) for patients with stage A, B, and C, respectively. 1.1% (0.0-2.7), 3.4% (1.0-6.3) and 10.0% (2.8-16.3) experienced HFH as their first event, whereas 37.3% (30.2-44.4), 49.7% (41.6-57.8) and 54.8% (43.4-66.2) were admitted for non-CV causes as their first event. CONCLUSION: The risk of HFH, IHD, stroke and all-cause death increased with severity of HF stage, and 10% of patients with undiagnosed HF stage C were admitted for HF within 3 years. However, the risk of non-CV hospitalizations was greater compared to the risk of experiencing HFH.

Importance of diagnostic setting in determining mortality in patients with new-onset heart failure: temporal trends in Denmark from 1997 to 2017.

AIM: To investigate temporal trends in inpatient vs. outpatient diagnosis of new-onset heart failure (HF) and the subsequent risk of death and hospitalization. METHODS AND RESULTS: Using nationwide registers, 192 581 patients with a first diagnosis of HF (1997-2017) were included. We computed incidences of HF, age-standardized mortality rates, and absolute risks (ARs) of death and hospitalization (accounting for competing risk of death) to understand the importance of the diagnosis setting in relation to subsequent mortality and hospitalization. The overall incidence of HF was approximately the same (170/100 000 persons) every year during 1997-2017. However, in 1997, 77% of all first diagnoses of HF were made during a hospitalization, whereas the proportion was 39% in 2017. As inpatient diagnoses decreased, outpatient diagnoses increased from 23% to 61%. Outpatients had lower mortality and hospitalization rates than inpatients throughout the study period, although the 1-year age-standardized mortality rate decreased for each inpatient (24 to 14/100-person) and outpatient (11 to 7/100-person). One-year and five-year AR of death decreased by 11.1% and 17.0%, respectively, for all HF patients, while the risk of hospitalization for HF did not decrease significantly (1.13% and 0.96%, respectively). CONCLUSION: Between 1997 and 2017, HF changed from being primarily diagnosed during hospitalization to being mostly diagnosed in the outpatient setting. Outpatients had much lower mortality rates than inpatients throughout the study period. Despite a significant decrease in mortality risk for all HF patients, neither inpatients nor outpatients experienced a reduction in the risk of an HF hospitalization.