Mortality, outcomes, costs, and use of medicines following a first heart failure hospitalization: EVOLUTION HF

Background: There are few contemporary data on outcomes, costs, and treatment following a hospitalization for heart failure (hHF) in epidemiologically representative cohorts. Objectives: The study sought to describe rehospitalizations, hospitalization costs, use of guideline-directed medical therapy (GDMT) (renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors), and mortality after hHF. Methods: EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational, longitudinal cohort study using data from electronic health records or claims data sources in Japan, Sweden, the United Kingdom, and the United States. Adults with a first hHF discharge between 2018 and 2022 were included. One-year event rates per 100 patient-years (ERs) for death and rehospitalizations (with a primary diagnosis of heart failure (HF), chronic kidney disease [CKD], myocardial infarction, stroke, or peripheral artery disease) were calculated. Hospital health care costs were cumulatively summarized. Cumulative GDMT use was assessed using Kaplan-Meier estimates. Results: Of 263,525 patients, 28% died within the first year post-hHF (ER: 28.4 [95% CI: 27.0-29.9]). Rehospitalizations were mainly driven by HF (ER: 13.6 [95% CI: 9.8-17.4]) and CKD (ER: 4.5 [95% CI: 3.6-5.3]), whereas the ERs for myocardial infarction, stroke, and peripheral artery disease were lower. Health care costs were predominantly driven by HF and CKD. Between 2020 and 2022, use of renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists changed little, whereas uptake of sodium-glucose cotransporter-2 inhibitors increased 2- to 7-fold. Conclusions: Incident post-hHF rehospitalization risks and costs were high, and GDMT use changed little in the year following discharge, highlighting the need to consider earlier and greater implementation of GDMT to manage risks and reduce costs

Association of lipid-related genetic variants with the incidence of atrial fibrillation: The AFGen consortium

Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04). Conclusions In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF

Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium

Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98–1.03); 0.98 (0.96–1.01); 0.98 (0.95–1.02); 0.99 (0.97–1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97–1.03); 1.01 (0.99–1.04). Conclusions: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF

Novel risk factors for atrial fibrillation in an urban population

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population, and a major cause of morbidity and mortality. Low-grade inflammation, erythrocyte volume variation, and subclinical atherosclerosis have repeatedly been associated with cardiovascular disease, but it remains unclear whether these risk factors are also associated with incident AF. This thesis is based on four epidemiological papers. Paper I-II included subjects from the Malmö Preventive Project (n=22 444, aged 26-61 years), followed during a mean follow-up time of 25 years. Paper III-IV included subjects from the Malmö Diet and Cancer Study (n=30 477, aged 44-74 years), followed during mean follow-up of 13.6 and 15.3 years respectively. Cases of incident AF were retrieved by linkage with the Swedish Hospital Discharge Register and the Swedish Cause of Death Register. Participants in Paper I-II underwent measurements of inflammation-sensitive proteins (ISPs) and genotyping of polymorphisms in the ceruloplasmin gene (CP). Red blood cells distribution width (RDW) was measured in participants of Paper III. Carotid intima-media thickness (IMT) was measured in participants of Paper IV. All subjects were without history of AF, myocardial infarction and heart failure at study entry. A score of five ISPs (ceruloplasmin, fibrinogen, haptoglobin, orosomucoid and α1-antitrypsin) were significantly associated with incidence of AF. Plasma levels of ceruloplasmin were associated with incidence of AF. Genetic polymorphisms in the promoter of the ceruloplasmin gene were associated with elevated plasma levels of ceruloplasmin. One of these polymorphisms was also associated with incidence of AF, suggesting a causal relationship between ceruloplasmin and AF. RDW and carotid IMT were both independently associated with incidence of AF. In conclusion, this thesis shows that ceruloplasmin, RDW and carotid IMT are all factors that may predict future events of AF in the general population. Further studies are needed to elucidate the causal pathway between ceruloplasmin and AF

Inflammation-sensitive proteins and risk of atrial fibrillation: a population-based cohort study.

Low-grade inflammation has been repeatedly associated with cardiovascular diseases but the relationship with incidence of atrial fibrillation (AF) remains unclear. We explored the association between elevated plasma levels of inflammation-sensitive proteins (ISPs) and incidence of AF in a population-based cohort. Plasma levels of five ISPs (fibrinogen, haptoglobin, ceruloplasmin, α(1)-antitrypsin and orosomucoid) and two complement factors (C3 and C4) were measured in 6,031 men (mean age 46.8 years) without history of myocardial infarction, heart failure, stroke or cancer. Incidence of hospitalizations due to AF during a mean follow-up of 25 years was studied both in relation to individual inflammatory proteins and the number of elevated ISPs. During follow-up, 667 patients were hospitalized with a diagnosis of AF. After adjustment for potential confounding factors, the hazard ratios (HR) for AF were 1.00 (reference), 1.08 (95% CI: 0.88-1.31), 1.07 (CI: 0.84-1.36), and 1.40 (CI: 1.12-1.74), respectively, in men with none, one, two and three or more ISPs in the 4th quartile (P for trend = 0.007). Ceruloplasmin was the only individual ISP significantly associated with incidence of AF after adjustment for confounding factors (HR 1.17 per standard deviation, 95% CI: 1.08-1.26). In conclusion, a score of five ISPs was associated with long-term incidence of hospitalizations due to AF in middle-aged men. Of the individual ISPs, a significant association was observed for ceruloplasmin, a protein previously associated with copper metabolism and oxidative stress

Incidence of Coronary Events and Case Fatality Rate in Relation to Blood Lymphocyte and Neutrophil Counts.

OBJECTIVE: Elevated levels of blood leukocytes have been associated with acute coronary events (CEs), but data on leukocyte subclasses are limited. This study aimed to explore whether blood lymphocyte and neutrophil counts are associated with incidence of CEs and with fatal outcome in subjects who subsequently experienced a first CE. METHODS AND RESULTS: Neutrophil and lymphocyte counts were measured in 27 419 subjects from the general population without a history of CEs, heart failure, or atrial fibrillation. Incidence of CEs was studied in relation to leukocyte counts during a mean follow-up of 13.6 years. Neutrophil but not lymphocyte counts were significantly associated with incidence of CEs. After adjustments for confounding factors, the hazard ratios (95% confidence interval) were 1.00 (reference), 1.07 (0.94-1.23), 1.09 (0.95-1.25), and 1.39 (1.22-1.59) for subjects with neutrophils in the first, second, third, and fourth (highest) sex-specific quartiles, respectively (P for trend <0.001). Of the 1965 subject who had a CE, 471 subjects died on the first day of the CE, in- or outside hospital. The proportions of subjects who died the first day were 19%, 21%, 25%, and 28%, respectively in the first, second, third, and fourth quartiles (P for trend <0.001). CONCLUSIONS: Increased neutrophil counts are associated with incidence of CEs and increased case-fatality rate after a CE

Ceruloplasmin and atrial fibrillation: evidence of causality from a population-based Mendelian randomization study.

Inflammatory diseases and inflammatory markers secreted by the liver, including C-reactive protein (CRP) and ceruloplasmin, have been associated with incident atrial fibrillation (AF). Genetic studies have not supported a causal relationship between CRP and AF, but the relationship between ceruloplasmin and AF has not been studied. The purpose of this Mendelian randomization study was to explore whether genetic polymorphisms in the gene encoding ceruloplasmin are associated with elevated ceruloplasmin levels, and whether such genetic polymorphisms are also associated with the incidence of AF

Red blood cell distribution width is associated with incidence of atrial fibrillation.

Red blood cell distribution width (RDW), a measure of variation in erythrocyte volume, has been associated with several cardiovascular disorders, but the relationship with atrial fibrillation (AF) remains unclear. We investigated the association between RDW and incidence of first hospitalization due to AF in a population-based cohort

Response to Letter to the Editor 'Red cell distribution width in patients with atrial fibrillation'

RDW is a new and easily available risk marker for adverse cardiovascular outcomes and we agree that this may encourage a wider use in clinical practice. As pointed out by Balta et al [2], the underlying causal links are unclear. The causal links could hypothetically involve some of the factors mentioned by Balta et al [2], but also properties of the red cells per se. This article is protected by copyright. All rights reserved

Carotid intima-media thickness is associated with incidence of hospitalized atrial fibrillation.

Carotid intima-media thickness (IMT) is a measure of arterial thickening and a risk predictor for myocardial infarction and stroke. It is unclear whether IMT also predicts atrial fibrillation (AF). We explored the association between IMT and incidence of first AF hospitalization in a population-based cohort