Risk Of Incident Heart Failure Research Articles

Risk of Incident Heart Failure and Heart Failure Subtypes in Patients with Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD) including heart failure (HF). However, little is known regarding the relative risks of heart failure subtypes such as HF with preserved (HFpEF) or reduced ejection fraction (HFrEF) in RA compared to non-RA. We identified RA patients and matched non-RA comparators among participants consenting to broad research from two large academic centers. We identified incident HF and categorized HF subtypes based on ejection fraction (EF) closest to the HF incident date. Covariates included age, sex, and established CVD risk factors. Cox proportional hazards models were used to estimate the hazard ratios (HR) for incident HF and HF subtypes. We studied 1445 RA patients and 4335 matched non-RA comparators (mean age 51.4 and 51.7 years, 78.7% female). HFpEF was the most common HF subtype in both groups (65% in RA vs. 59% in non-RA). RA patients had a HR of 1.79 (95% CI: 1.38-2.32) for incident HF compared to those without RA after adjusting for CVD risk factors. RA patients had a higher rate of HFpEF (HR 1.99, 95% CI: 1.43 - 2.77), but there was no statistical difference in HFrEF rate (HR 1.45, 95% CI 0.81 - 2.60). RA was associated with higher rate of HF overall compared to non-RA, even after adjustment for established CVD risk factors. The elevated risk was driven by HFpEF, supporting a role for inflammation in HFpEF and highlighting potential opportunities to address this excess risk in RA.

Abstract 4116714: Macrophage Colony Stimulating Factor as a Causal Metabolic Mediator of Cardiovascular Disease: An Observational and Mendelian Randomization Analysis

Background: Macrophage biology plays a key role in the pathogenesis of atherosclerosis and circulating macrophage colony-stimulating factor (M-CSF) is a marker of macrophage activity. However, there is conflicting evidence regarding its role as a mediator of cardiovascular disease. Methods: We evaluated the association between plasma M-CSF concentration with myocardial infarction, stroke, heart failure and mortality in a large substudy involving 9992 participants drawn from 14 countries and followed for a median period of 9.8 years (Interquartile Range 8.9 years - 11.4 years) utilizing a nested case-cohort design in the Prospective Urban Rural Epidemiology (PURE) study. We then conducted a two-sample Mendelian randomization (MR) analysis to evaluate the upstream determinants (using genome wide association data from the PURE biobank and publicly available consortia) and downstream effects on clinical events.. Results: The strongest causal upstream determinant of M-CSF concentration was body mass index (BMI), which showed a positive association with plasma M-CSF concentration (Beta: 0.17 SD increase; 95% CI: 0.08 - 0.27). In a survival analysis, M-CSF was independently associated with increased incident myocardial infarction (HR: 1.25 per 1 SD M-CSF increase; 95% CI: 1.13-1.38), stroke (HR: 1.17; 95% CI:1.04-1.32), and heart failure (HR: 1.34; 95% CI: 1.15-1.56) and other cardiovascular disease risk factors. Circulating M-CSF concentration also showed a strong association with long-term risk of overall mortality (HR: 1.44; 95% CI: 1.39-1.60). Mendelian randomization analyses confirmed that increased M-CSF was associated with increased risk of MI, heart failure, and ischemic stroke (specifically large artery atherosclerotic and cardioembolic stroke). Conclusions: M-CSF is a strong causal driver of cardiovascular disease morbidity whose concentration is causally influenced by body mass index. Our analysis suggests a role for macrophage activity in mediating the relationship between body mass index and cardiovascular disease outcomes.

Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score. Results: Of the 2071 patients (mean age at HSCT 55.5 + 12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint. Conclusion: LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.

A liberal blood transfusion strategy is safe in patients with myocardial infarction, anemia, and heart failure: lessons from MINT

Abstract Background In patients with acute myocardial infarction (MI) and anemia, the Myocardial Ischemia and Transfusion (MINT) trial found a trend toward increased 30-day death or recurrent MI with a restrictive compared with a liberal blood transfusion strategy. Patients with and without heart failure (HF) may respond differently to blood transfusion. Purpose To characterize the effects of restrictive vs. liberal transfusion strategies on clinical outcomes in patients with MI and anemia with and without baseline HF. Methods In the MINT trial, 3504 patients with MI and hemoglobin <10 g/dL were randomized to restrictive (7-8 g/dL) or liberal (10 g/dL) transfusion thresholds. We compared outcomes between patients with and without baseline HF, defined as any history of HF, acute HF, or baseline left ventricular ejection fraction (LVEF) <45%. Outcomes included death or incident HF, death or recurrent MI, death, and incident HF, all at 30 days. Results Compared with patients without baseline HF (n=1633), patients with baseline HF (overall n=1871 (history of HF n=1066, acute HF n=780, LVEF <45% n= 1099) were older, more frequently male and Black, and had higher rates of prior PCI, diabetes, and hypertension. In the restrictive strategy, patients with and without baseline HF received an average of 0.63 and 0.80 units of blood and had a median LOS of 6 and 4 days, respectively. In the liberal strategy, patients with and without baseline HF received an average of 2.44 and 2.49 units of blood and had a median LOS of 5 and 4 days, respectively. Patients with baseline HF had higher rates of death or incident HF (18.0% vs. 10.0%, risk ratio [RR]=1.79 [95% confidence interval {CI} 1.50-2.13]), death or recurrent MI (17.6% vs. 13.5%, RR=1.31 [95% CI 1.12-1.53]), and death (10.5% vs. 7.5%, RR 1.41 [95% CI 1.14-1.75]). Among patients with baseline HF, a restrictive transfusion strategy resulted in a trend toward an increase in death or HF and death or MI compared with a liberal transfusion strategy (Table, Figure). Among patients without baseline HF, the risk of incident HF was lower with restrictive than with liberal transfusion strategy. Conclusions Among patients with MI and anemia, a restrictive transfusion strategy resulted in a greater increase in death or HF, death or MI, and death in patients with baseline HF than in patients without baseline HF. A liberal transfusion strategy is safe for patients with MI and anemia, including those with prior or acute HF.TableFigure

Serum metabolomics improve risk stratification for incident heart failure

Abstract Background The prediction and early detection of heart failure (HF) is vital to reduce its substantial impact on quality of life, survival and healthcare expenditure. Current incident HF risk stratification strategies achieve only modest performance. Moreover, state-of-the-art risk scores focus on commonly acknowledged clinical risk factors, thus necessitating the integration of heterogenous data sources and prioritizing individuals with obvious risk constellations. Purpose Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance (1H-NMR) spectroscopy) for incident HF. Methods Leveraging data of n = 68,311 individuals and > 0.8 million person-years of follow-up from the UK Biobank (UKB) cohort, we (I) evaluated the association of individual metabolites with incident HF via fitting of per-metabolite COX proportional hazards models and (II) trained and validated elastic net (EN) models to predict incident HF using the serum metabolome. Discriminative performance was benchmarked against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF, PCP-HF). External validation was conducted in the independent FINRISK study. Results Several metabolites were independently associated with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈ 80 % feature reduction). The addition of metabolomics to PCP-HF improved predictive performance (Harrel’s C: 0.768 vs. 0.755, ΔC = 0.013 (95% confidence interval (CI) 0.004 – 0.022), continuous net reclassification improvement (NRI) = 0.287 (95% CI 0.200 – 0.367), relative integrated discrimination improvement (IDI): 17.47 % (95% CI 9.463 - 27.825)). Simplified models only including age, sex and metabolomics performed almost as well as the PCP-HF model (Harrel’s C: 0.745 vs. 0.755, ΔC = 0.010 (95% CI -0.004 - 0.027), continuous NRI: 0.097 (95% CI -0.025 - 0.217), relative IDI: 13.445 % (95% CI -10.608 - 41.454)). Risk and survival stratification was improved by integrating metabolomics. External validation within FINRISK revealed similar patterns using the original model coefficients. Conclusions Serum metabolomics improve the prediction of incident HF risk. Scores obtained from the combination of age, sex and metabolomics exhibit similar predictive power as clinical risk models. Offering serum metabolomics to a middle-aged cohort might significantly improve HF risk stratification, thus facilitating preventive efforts. Via a single blood draw, serum metabolomics displays a highly cost- and time-effective, standardizable, and scalable alternative to clinical risk scores involving physical measurements and history taking in addition to clinical chemistry.Relative performance (test split)ROC & DCA plots (test split)

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Education level and the incidence of heart failure, acute myocardial infarction, and stroke in patients with atrial fibrillation

Abstract Background Education level is an important socioeconomic factor affecting the incidence, symptoms, and treatment of atrial fibrillation (AF). Despite this, data on the association between education level and the incidence of major AF consequences – heart failure (HF), acute myocardial infarction (AMI), and stroke – are limited. Aim To investigate the association between education level and the risk of HF, AMI, and stroke in patients hospitalized with AF. Methods This retrospective cohort study is based on data generated by crosslinking of several Swedish national registries. All patients hospitalized between 1998 and 2003 with a diagnosis of AF were included. The relative risk for incident HF, AMI, and stroke were assessed according to education level categories during a 5–year follow–up. Education levels were categorised as primary, secondary, and academic. Kaplan-Meier curves and Cox regression models adjusted for age, sex, time of AF diagnosis, and the variables of Charlson´s Comorbidity Index were used to estimate the relative risk of the examined outcomes. Hazard ratios (HR) with 95% confidence intervals (CI) were used as estimate of associations and statistical significance level was 5%. Results The study included 263,172 patients (56.2% male; mean age 72.5±10.4 years). There was a statistically significant dose-dependent association between education level and the risk of AMI and HF in both sexes. Compared to primary education, the HR for AMI was 0.89 (95% CI: 0.85-0.93) for secondary education and 0.71 (95% CI: 0.65-0.78) for academic education in women; and 0.91 (95% CI: 0.87-0.94) for secondary education and 0.75 (95% CI: 0.71-0.80) for academic education in men. The relative risk for HF was similar, with HRs of 0.96 (95% CI: 0.93-1.00) for secondary and 0.82 (95% CI: 0.77-0.87) for academic education in women, and HRs of 0.93 (95% CI: 0.90-0.96) for secondary and 0.76 (95% CI: 0.72-0.80) for academic education in men. Patients with academic education had a significantly lower risk for stroke compared to those with primary education (HR 0.77 (95% CI: 0.71-0.84) in women; HR 0.84 (95% CI: 0.79-0.90) in men), while patients with secondary education did not have a significantly different relative risk for stroke compared to those with primary education. Conclusion Secondary and academic education levels were associated with a significantly lower risk of HF and AMI in both women and men with AF compared to primary education. Furthermore, academic education was associated with a lower risk of stroke. In conclusion, , higher education levels were associated with a lower 5-year risk of HF, AMI, and stroke compared to primary education

Cardiac contractility index, a novel biomarker of incident heart failure amongst people with normal left ventricular ejection fraction in the UK Biobank

Abstract Background Cardiac contractility index (CCI) is a simple non-invasive measure of myocardial contractility defined by systolic blood pressure divided by indexed left ventricular end-systolic volume. Although left ventricular ejection fraction (LVEF) is essential for phenotyping patients with suspected heart failure (HF), it is load dependent and insensitive to subtle subclinical ventricular dysfunction. Left ventricular (LV) strain, although more sensitive at detecting subtle disturbances in myocardial function, also does not reflect loading conditions and dependency on image quality and inter-vendor variability limit widespread use. The ability of CCI to identify patients with subclinical left ventricular dysfunction at risk of developing HF is unknown. Purpose We aimed to: 1) explore the relationship between CCI with conventional imaging biomarkers of LV systolic dysfunction and 2) assess whether CCI could identify those at increased risk of incident HF in people without pre-existing left ventricular dysfunction in the UK Biobank imaging study. Methods We explored the relationship between CCI and laboratory and imaging biomarkers of systolic function, including LVEF and LV strain. Scatter plots were constructed for CCI with LVEF and LV strain. Pearson’s coefficients (r) and coefficient of determination (r2) were calculated to assess for correlations. People with sex-specific thresholds of abnormally low LVEF derived from within the same cohort (<48% for men, and <51% for women) were then excluded. CCI was then dichotomised as being high or low based its median value (4.4 mmHg/ml/m2). Age-sex adjusted Cox proportional hazards ratios (HR) with 95% CIs were estimated for the primary outcome of incident HF (derived from linked national digital registries) in addition to modelling with restricted cubic splines. Results We included 38,215 people (median age 55 years, 48% men). There was moderate correlation between CCI with LVEF (r=0.53 [0.53-0.54], R2=0.29; p<0.001), LV global circumferential strain (r=-0.50 [-0.50- -0.49], R2=0.25; p<0.001) and radial strain (r=-0.49 [0.48-0.50], R2=0.24; p<0.001), although was only weekly correlated with LV global longitudinal strain (r=-0.19 [-0.20- -0.18], R2=0.03; p<0.001) (Figure 1A). Using sex-specific thresholds 33,739 (88.3%) had a normal LVEF. During 195,584 person-years of follow-up (median 5.5 years), a total of 221 (0.7%) participants developed HF. Age-sex adjusted low CCI at baseline was associated with an increased risk of incident HF (adjusted HR 1.33 [1.01-1.75]; p=0.043). The association between CCI and incident HF was curvilinear (Figure 1B). Conclusions CCI identifies people with subclinical left ventricular systolic dysfunction at risk of developing incident heart failure.

Comparison of heart failure risk assessment tools among cancer survivors

BackgroundCancer survivors have an increased risk of incident heart failure (HF) attributable to shared risk factors and cancer treatment-induced cardiac dysfunction. Selection for HF screening depends on risk assessment, but the optimal means of assessing risk is undefined. We undertook a comparison of HF risk calculators among survivors.MethodsIn this study from the UK Biobank, cancer and HF diagnoses were determined based on the International Classification of Diseases (ICD)-10 code and non-cancer participants were included as controls. Participants’ risk of incident HF was determined using the Heart Failure Association-International Cardio-oncology Society (HFA-ICOS), the Atherosclerosis Risk in Communities (ARIC-HF) and the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF). The predictive performances of each were compared using the area under the curve (AUC).ResultsAfter propensity matching with age and sex, 9,232 survivors from breast cancer or lymphoma (mean age 59.9 years, 87.8% female), and 23,800 survivors from other cancer types (mean age 59.1 years, 85.8% female) were included in the analysis. The discriminative value for HFA-ICOS (AUC 0.753 [95%CI: 0.739–0.766]) and ARIC-HF (0.757 [95%CI: 0.744–0.770]) were similar, and superior to PCP-HF (0.717 [95%CI: 0.702–0.732]). The overall performance for each risk score was better among participants in other cancer types than those with breast cancer and lymphoma.ConclusionsHFA-ICOS and ARIC-HF outperformed the PCP-HF among cancer- and non-cancer cohort, although all showed modest discrimination for incident HF to be applied to clinical practice. A cancer-specific HF prediction tool could facilitate HF prevention among survivors.

Machine learning in the prevention of heart failure.

Heart failure (HF) is a global pandemic with a growing prevalence and is a growing burden on the healthcare system. Machine learning (ML) has the potential to revolutionize medicine and can be applied in many different forms to aid in the prevention of symptomatic HF (stage C). HF prevention currently has several challenges, specifically in the detection of pre-HF (stage B). HF events are missed in contemporary models, limited therapeutic options are proven to prevent HF, and the prevention of HF with preserved ejection is particularly lacking. ML has the potential to overcome these challenges through existing and future models. ML has limitations, but the many benefits of ML outweigh these limitations and risks in most scenarios. ML can be applied in HF prevention through various strategies such as refinement of incident HF risk prediction models, capturing diagnostic signs from available tests such as electrocardiograms, chest x-rays, or echocardiograms to identify structural/functional cardiac abnormalities suggestive of pre-HF (stage B HF), and interpretation of biomarkers and epigenetic data. Altogether, ML is able to expand the screening of individuals at risk for HF (stage A HF), identify populations with pre-HF (stage B HF), predict the risk of incident stage C HF events, and offer the ability to intervene early to prevent progression to or decline in stage C HF. In this narrative review, we discuss the methods by which ML is utilized in HF prevention, the benefits and pitfalls of ML in HF risk prediction, and the future directions.

The Impact of Hormone Replacement Therapy on the Riskof Heart Failure in Postmenopausal Women: A Meta-Analysis of Clinical and Observational Studies.

The relationship between heart failure (HF) and hormone replacement therapy (HRT) in postmenopausal women remains unclear. This paper aimed to elucidate the association between HRT and HF outcomes in postmenopausal women by scrutinizing evidence from clinical trials and observational studies. The meta-analysis was systematically executed following the PRISMA guidelines to include studies identified from the electronic databases, including PubMed, EMBASE, EBSCO, ICTRP, and NIH clinical trials. The primary endpoint of the effect comprised risk ratios (RR) for HF incidence and mortality, attended by 95% confidence intervals (CIs). The risk of bias was assessed employing the Cochrane Risk of Bias 2 (RoB2) tool for clinical trials and the Newcastle-Ottawa Scale (NOS) for observational studies. The search yielded a total of eight reports, originating from six individual studies, for inclusion in the current study, and 25 047 participants were included. The meta-analysis demonstrated no remarkable association between HRT and the incidence of HF in postmenopausal women (RR: 1.07, 95% CI: 0.91-1.25, p = 0.37). However, a significant reduction in all-cause mortality was observed among post-menopausal HF patients who received HRT (RR: 0.65, 95% CI: 0.49-0.87, p = 0.003). In age-related subgroup analyses, no significant change in the risk of HF was noticed among participants on HRT. The findings of this paper demonstrate that HRT use is not associated with a significant increase in the risk of incident HF. This meta-analysis also suggests a benefit in all-cause mortality when HRT is administered to postmenopausal women with HF.

Uric acid and risk of incident heart failure in individuals with cardiovascular disease

Background and aimsUric acid has been positively associated with the risk of developing heart failure in the general population. Nevertheless, it remains unclear whether hyperuricemia is an independent risk factor for heart failure and further contributes to the risk of heart failure among the already at-risk cardiovascular disease (CVD) population. This study aimed to evaluate the association between uric acid and incident heart failure in individuals with established CVD. Methods and resultsIncluded were 18,438 adults with established CVD but free of heart failure at baseline, from the Kailuan Study. Incident heart failure cases were ascertained by medical records. Cause-specific Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of heart failure according to uric acid tertiles. Over a median follow-up of 6.1 years, we identified 1215 incident heart failure cases. Higher uric acid was associated with a higher risk of incident heart failure, with adjusted HR for the last vs. first tertile of 1.50 (95%CI:1.30–1.73). Higher uric acid concentrations were associated with an increased risk of heart failure in individuals with coronary heart disease, atrial fibrillation, and ischemic stroke, but not in those with hemorrhagic stroke. Moreover, the observed association between uric acid and heart failure risk was more pronounced in individuals diagnosed with heart failure with reduced ejection fraction subtype compared with heart failure with preserved ejection fraction. ConclusionsIn individuals with CVD, uric acid was positively associated with the risk of heart failure, in a dose-response manner.

Comparison of the correlation of creatinine- and cystatin C–Based estimated GFR and their differences with new-onset heart failure in a community-based population with type 2 diabetes

AimsThis study aimed to investigate the impact of different estimated glomerular filtration rate (eGFR) values like cystatin C-based eGFR (eGFRcys), creatinine-based eGFR (eGFRcr), and their difference (eGFRdiff; eGFRcys -eGFRcr), on the incidence of heart failure (HF) in patients with type 2 diabetes(T2D).MethodsBeing a prospective cohort study, it included 7,967 patients with T2D who underwent serum creatinine and cystatin C tests as part of the Kailuan Group’s 6th annual health examination (2016). Subsequently, eGFRcys, eGFRcr, and eGFRdiff were calculated. Patients were categorized into three groups: negative (<-15 mL/min/1.73 m2), midrange (-15 to 15 mL/min/1.73 m2), and positive (> 15 mL/min/1.73 m2) eGFRdiff groups, respectively. Furthermore, the relationship between the various eGFR measurements and new-onset HF were studied using Cox proportional hazards regression, and the potential improvement in predictive capability was evaluated by adding these eGFR metrics to established HF risk models.ResultsAmong 7967 participants with mean age of 60.51 years, there were 20.92% women and 79.08% men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73m2 in 41.3% of participants. During a median follow-up period of 3.76 years, there were 172 (2.16%) new HF cases and 517 (6.49%) all-cause deaths. The cumulative incidence of HF in the midrange, negative, and positive eGFRdiff groups was 1.74%, 4.10%, and 0.61%, respectively (p < 0.001). In multivariable adjusted models, participants in the negative eGFRdiff group had higher risk of HF compared with the midrange eGFRdiff group (HR, 2.15; 95% CI, 1.57–2.94). Conversely, participants in the positive eGFRdiff group had lower risk for HF (HR, 0.40; 95% CI, 0.17–0.93). And each 15 mL/min/ 1.73 m2 higher eGFRdiff was associated with 34% (HR, 0.66; 95% CI, 0.58 − 0.47)lower risk of incident HF. The predictive capacity for HF risk in diabetic individuals was enhanced by adding eGFRcys or eGFRdiff to established HF risk models, with eGFRcys showing more significant additional predictive value.ConclusionThese findings suggest that large differences between eGFRcys and eGFRcr were common in community-based population with T2D. Different eGFR metrics can independently predict HF incidence in patients with T2D. Additionally, metrics like eGFRcys and eGFRdiff provide significant predictive value for HF risks beyond traditional risk factors, with eGFRcys showing more pronounced benefits in such cases.

Associations of age at diagnosis of breast cancer with incident myocardial infarction and heart failure: A prospective cohort study.

The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer. Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed. A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19-1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18-1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer. Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases. This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466).

Associations of objective sleep duration and physical activity with risk of heart failure: A prospective cohort study

ObjectiveThis study aimed to investigate the independent and joint associations of accelerometer-derived sleep duration and physical activity (PA) in different intensities with the risk of incident heart failure (HF). MethodsThe study included 89,572 participants (mean age 62.2 ± 7.8 years, 42.8% male) from the UK Biobank. Sleep duration (short: <6 h/day; normal: 6–8 h/day; long: >8 h/day) and PA [total PA, light PA (LPA), moderate-to-vigorous PA (MVPA), vigorous PA (VPA)] were measured using accelerometers over 7 days. MVPA and VPA were categorized according to the World Health Organization's recommended levels, while LPA and total PA were categorized based on the median. HF cases were identified through hospital records or death registries. ResultsOver a 7-year follow-up period, 1324 participants (2.1%; incidence rate, 2.1 per 1000 person-years) developed HF. Short, but not long, sleep duration was linked to a 33% increased risk of HF [hazard ratio (HR) 1.33, 95% confidence interval (CI): 1.11–1.59]. This increased risk associated with short sleep could be mitigated by increasing PA, especially to the levels of recommended MVPA or VPA. In joint analyses, compared to participants meeting the recommended MVPA and with normal sleep duration, those not meeting the MVPA recommendation and with short sleep had the highest HF risk (HR 1.78, 95% CI: 1.42–2.25). ConclusionsAccelerometer-derived short, but not long, sleep duration was associated with a higher risk of incident HF. Engaging in sufficient PA, especially recommended MVPA or VPA, can partially mitigate this risk.

Relationship of the trajectory of the triglyceride-glucose index with heart failure: the Kailuan study

BackgroundA high triglyceride-glucose index (TyG) is associated with a higher risk of incident heart failure. However, the effects of longitudinal patterns of TyG index on the risk of heart failure remain to be characterized. Therefore, in the present study, we aimed to characterize the relationship between the trajectory of TyG index and the risk of heart failure.MethodsWe performed a prospective study of 56,149 participants in the Kailuan study who attended three consecutive surveys in 2006–2007, 2008–2009, and 2010–2011 and had no history of heart failure or cancer before the third wave survey (2010–2011). The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2], and we used latent mixture modeling to characterize the trajectory of the TyG index over the period 2006–2010. Additionally, Cox proportional risk models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for incident heart failure for the various TyG index trajectory groups.ResultsFrom 2006 to 2010, four different TyG trajectories were identified: low-stable (n = 13,554; range, 7.98–8.07), moderate low-stable (n = 29,435; range, 8.60–8.65), moderate high-stable (n = 11,262; range, 9.31–9.30), and elevated-stable (n = 1,898; range, 10.04–10.25). A total of 1,312 new heart failure events occurred during a median follow-up period of 10.04 years. After adjustment for potential confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident heart failure for the elevated-stable, moderate high-stable, and moderate low-stable groups were 1.55 (1.15, 2.08), 1.32 (1.08, 1.60), and 1.17 (0.99, 1.37), respectively, compared to the low-stable group.ConclusionsHigher TyG index trajectories were associated with a higher risk of heart failure. This suggests that monitoring TyG index trajectory may help identify individuals at high risk for heart failure and highlights the importance of early control of blood glucose and lipids for the prevention of heart failure.

Systolic blood pressure time in target range within 24 hours and incident heart failure: insights from the real-world setting.

Systolic blood pressure (SBP) time in target (TTR) over months were associated with lower risk of adverse clinical outcomes in hypertensive patients, whether short-term of 24-h SBP TTR was effective in predicting heart failure (HF) risk in the general population remained unclear. This prospective study aimed to investigate the association of 24-h SBP TTR with HF in the real-world settings. Based on Kailuan study, 24-h SBP target range defined as 110-140 mmHg was calculated with linear interpolation. Among 5152 participants included in the analysis, 186 (3.61%) cases of incident HF occurred during a median follow-up of 6.96 years. Compared with participants with SBP TTR of 0 to <25%, those with TTR of 75% to 100% had 47% lower risk of HF (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.32-0.89). The restricted spline curve depicted an inverse relationship between SBP TTR and incident HF. Additionally, the addition of SBP TTR, rather than mean SBP and SBP variation, to a conventional risk model had an incremental effect on the predictive value for HF, with integrated discrimination improvement value of 0.31% (P = 0.0003) and category-free net reclassification improvement value of 19.79% (P = 0.0081). Higher SBP TTR was associated with a lower risk of incident HF. Efforts to attain SBP within 110 to 140 mmHg may be an effective strategy to prevent HF.

Association between cardiac time intervals and incident heart failure after acute coronary syndrome

BackgroundCardiac time intervals are sensitive markers of myocardial dysfunction that predispose to heart failure (HF). We aimed to investigate the association between cardiac time intervals and HF in patients with acute coronary syndrome (ACS).MethodsThis study included 386 ACS patients treated with percutaneous coronary intervention (PCI). Patients underwent an echocardiography examination a median of two days after PCI. Cardiac time intervals including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and systolic ejection time (ET), and myocardial performance index (MPI) were obtained by tissue Doppler echocardiography. The outcome was incident HF.ResultsDuring follow-up (median 4.3, IQR:1.0-6.7 years), 140 (36%) developed HF. In unadjusted analyses, IVRT was not associated with HF (HR 1.02 (0.95–1.10), p = 0.61, per 10ms increase), and neither was IVCT (HR 0.07 (0.95–1.22), p = 0.26, per 10ms increase). Increasing MPI was associated with a higher risk of HF (HR 1.20 (1.08–1.34), P = 0.001, per 0.1 increase), and so was decreasing ET (HR 1.13 (1.07–1.18), P < 0.001 per 10ms decrease). After multivariable adjustment for cardiovascular risk factors, MPI (HR 1.13 (1.01–1.27), P = 0.034) and ET (HR 1.09 (1.01–1.17), P = 0.025) remained significantly associated with incident HF. LVEF modified the association between ET and HF (p for interaction = 0.002), such that ET was associated with HF in patients with LVEF ≥ 36% (HR = 1.15 (1.06–1.24), P = 0.001, per 10ms decrease).ConclusionIn patients admitted with ACS, shortened ET and higher MPI were independently associated with an increased risk of incident HF. Additionally, ET was associated with incident HF in patients with LVEF above 36%.Graphical

Trajectory of C-Reactive Protein and Incident Heart Failure in Black Adults: The Jackson Heart Study.

Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization. JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (≥2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high. Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction (P>0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF (P<0.05). While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults.

Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF). We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors. In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race. In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF. URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.