Reduced Risk Of Heart Failure Research Articles

Dietary Factors and Cardiovascular Diseases: Comprehensive Insights from the National Health and Nutrition Examination Survey 2017-2020 and Mendelian Randomization Analysis.

Cardiovascular diseases (CVDs) are a major public health concern. The impact of dietary components on CVD risk has been recognized, but their interactions require further investigation. This study aimed to examine the associations between major nutrient intake and CVD risk and to assess potential causal relationships via Mendelian randomization. We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, with a sample size of 5464 adult participants. Nutrient intake was derived from two 24 h dietary recalls. Associations between four principal nutrients and CVD risk were evaluated via Mendelian randomization analysis. Additionally, weighted multivariable logistic regression analyses were performed to adjust for potential confounders, including age, sex, BMI, and other lifestyle factors. An observational analysis revealed that increased log-transformed dietary fat intake was associated with reduced heart failure risk (OR = 0.722, 95% CI: 0.549-0.954). Log-transformed protein intake was protective against heart failure (OR = 0.645, 95% CI: 0.471-0.889), coronary artery disease (OR = 0.684, 95% CI: 0.504-0.931), and stroke (OR = 0.747, 95% CI: 0.568-0.988). IVW-MR analyses confirmed causal relationships between relative fat intake and heart failure risk (OR = 0.766, 95% CI: 0.598-0.982, p = 0.035) and between protein intake and stroke risk (OR = 0.993, 95% CI: 0.988-0.998, p = 0.010). MR analysis also revealed causal relationships between relative fat intake and coronary artery disease risk and between relative protein intake and hypertension risk. Both the observational and Mendelian randomization studies indicated that dietary fat is inversely associated with heart failure risk and that protein intake is correlated with reduced stroke risk. Future studies should investigate the optimal balance of macronutrients for CVD prevention, explore potential mechanisms underlying these associations, and consider long-term dietary interventions to validate these findings.

Cardiovascular Risk Factors and Genetic Risk in Transthyretin V142I Carriers.

Nearly 3% to 4% of Black individuals in the United States carry the transthyretin V142I variant, which increases their risk of heart failure. However, the role of cardiovascular (CV) risk factors (RFs) in influencing the risk of clinical outcomes among V142I variant carriers is unknown. This study aimed to assess the impact of CV RFs on the risk of heart failure in V142I carriers. This study included self-identified Black individuals without prevalent heart failure from 6 TOPMed (Trans-Omics for Precision Medicine) cohorts, the REGARDS (Reasons for Geographic And Racial Differences in Stroke) study, and the All of Us Research Program. The cohort was stratified based on the V142I genotype and the number of CV RFs (hypertension, diabetes, obesity, and hypercholesterolemia). Adjusted Cox models were used to assess the association of heart failure with the V142I genotype and CV RF profile, taking noncarriers with a favorable CV RF profile as reference. The cross-sectional analysis, including 1,625 V142I carriers among 48,365 Black individuals, found that the prevalence of CV RFs did not vary by V142I carrier status. In the longitudinal analysis, there were 587 (3.2%) V142I carriers among 18,407 Black individuals (median age: 60 years [Q1-Q3: 52-68 years], 63.0% female). Among carriers, the heart failure risk was attenuated with a favorable (0 or 1 RF) CV RF profile (adjusted HR: 2.26; 95%CI: 1.58-3.23) compared with an unfavorable (3 or 4 RFs) CV RF profile (adjusted HR: 4.14; 95%CI: 2.79-6.14). A favorable CV RF profile lowers but does not abrogate V142I variant-associated heart failure risk. This study highlights the importance of having a favorable CV RF profile among V142I carriers for risk reduction of heart failure.

Causal Association of Chronic Venous Insufficiency and Cardiovascular Diseases: A Univariable and Multivariable Mendelian Randomization Study.

The causal relationship between chronic venous insufficiency (CVI) and cardiovascular diseases (CVDs) has yet to be elucidated. Herein, we implement Mendelian randomization (MR) analysis to investigate the causal association. A two-sample MR approach using genetic data from FinnGen and genome-wide association studies (GWAS) Catalog was applied to investigate the causal relationship between CVI and CVDs. This study assessed 77 single nucleotide polymorphisms (SNPs) as instrumental variables, employing random-effect inverse-variance-weighted MR, weighted median, Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Robust Adjusted Profile Score (RAPS) methods. Multivariable MR (MVMR) considered confounding factors. Genetically predicted CVI was associated with reduced heart failure risk (odds ratio (OR) = 0.96, 95% confidence interval (95% CI): 0.93-0.99, p = 0.025) and increased atrial fibrillation risk (OR = 1.06, 95% CI: 1.03-1.09, p = 0.0002). MVMR, adjusting for venous thromboembolism (VTE), lower limb ulceration, obesity, smoking, and alcohol, attenuated these associations. No significant links were found with hypertension, aortic aneurysm, coronary artery disease, myocardial infarction, valvular heart disease, or stroke. This MR study supports an association between CVI and CVDs, which may imply CVI should be monitored during the treatment of heart failure and atrial fibrillation.

The association of glycaemic risk factors and diabetes duration with risk of heart failure in people with type 2 diabetes: A systematic review and meta-analysis.

To conduct a systematic review in order to better understand the association of glycaemic risk factors and diabetes duration with risk of heart failure (HF) in individuals with type 2 diabetes (T2D). We identified longitudinal studies investigating the association of glycaemic factors (glycated haemoglobin [HbA1c], HbA1c variability, and hypoglycaemia) and diabetes duration with HF in individuals with T2D. Hazard ratios and odds ratios were extracted and meta-analysed using a random-effects model where appropriate. Risk of bias assessment was carried out using a modified Newcastle-Ottawa Scale. Egger's test along with the trim-and-fill method were used to assess and account for publication bias. Forty studies representing 4 102 589 people met the inclusion criteria. The risk of developing HF significantly increased by 15% for each percentage point increase in HbA1c, by 2% for each additional year of diabetes duration, and by 43% for having a history of severe hypoglycaemia. Additionally, variability in HbA1c levels was associated with a 20%-26% increased risk of HF for each unit increase in the metrics of variability (HbA1c standard deviation, coefficient of variation, and average successive variability). All included studies scored high in the risk of bias assessment. Egger's test suggested publication bias, with trim-and-fill analyses revealing a significant 14% increased risk of HF per percentage point increase in HbA1c. Glycaemic risk factors and diabetes duration significantly contribute to the heightened risk of HF among individuals with T2D. A reduction in risk of HF is anticipated with better management of glycaemic risk factors.

Abstract P121: Weight Loss is not a Major Mediator of GLP1-Receptor Agonists’ Risk Reduction in Heart Failure with Preserved Ejection Fraction

The cardioprotective effects of GLP1-Receptor Agonists (GLP1-RA) and SGLT2 Inhibitors (SGLT2i) are incompletely understood. We compared these two drug classes and their effect on HFpEF hospitalizations and examined the hypothesis that weight loss is a significant mediator of these agents’ HFpEF protection. Methods: Using the VA Informatics and Computing Infrastructure, we generated a national cohort of veterans with type 2 diabetes on metformin who initiated SGLT2i, GLP1-RA or Insulin Glargine for the first time from 1/1/18 to 12/31/21. The index date was the date of first outpatient prescription fill. We defined 6-month weight change as change from baseline weight (closest outpatient value prior to index date within 1 year) to 6 months (all averaged outpatient weights from index date to 6 months). Those with prior prescriptions for the study drugs from 1/1/08 and missing baseline or 6-month weights were excluded. HFpEF hospitalizations were defined by a previously-validated natural language processing algorithm using inpatient HF diagnostic codes and cardiac imaging dated closest to and within 180 days of the new code with ejection fraction ≥50%. Follow up was through 3/31/23. We performed mediation analyses to separate the direct effects (independent of 6-month weight change) and indirect effects (mediated through 6-month weight change) of the drug classes on time to HFpEF hospitalizations, adjusted for demographics, comorbidities, baseline labs and other medications, and diabetes severity. Results: Overall, 161,405 veterans initiated one of the study drugs and 105,439 had weight data. After excluding 760 veterans with HFpEF hospitalizations in the first 6 months, 104,679 were included in the analysis. Baseline demographics included mean age 64±11 years, 94% male and 75% white. Baseline BMI was 33±6 kg/m 2 . There were 1494 HFpEF hospitalizations/ 256,101 years of follow-up. Figure 1 shows weight over time by study drug class. Table 1 shows mediation analyses results. Conclusion: GLP1-RA lowered the risk of HFpEF hospitalizations versus the active comparator insulin glargine. This cardioprotection was not mediated by weight loss. GLP1-RA and SGLT2i show equivalent risk reduction. These agents' direct cardiac and vascular effects deserve further exploration.

Association between leukocyte telomere length and heart failure hospitalization based on the presence of the atrial fibrillation

Abstract Leukocyte telomere length (LTL) is a well-established biomarker linked to cardiovascular disease, with shorter LTL associated with increased severity of heart failure (HF) outcomes. It is also well known that atrial fibrillation (AF) and HF are closely related and often coexist. This study explores the relationship between LTL and hospitalization due to HF, considering both AF and non-AF patients within the UK Biobank cohort. Retrospective analysis of the UK Biobank dataset (n=451,552, mean age 57.0±8.1 years, 45.8% male) excluded individuals with pre-existing HF (n=12,162) and extreme/no LTL data (n=36,829). LTL was quantified using multiplex quantitative polymerase chain reaction. Among 445,895 participants without AF at enrollment, 2,851 were hospitalized for HF (mean age 63.1±5.8, 63.3% male), while 313 with AF (mean age 64.3±5.3, 68.4% male) experienced HF hospitalization. Shorter LTL correlated significantly with HF hospitalization in both non-AF (826.8±117.7 vs 797.9±115.5, P < 0.001) and AF groups (804.8±116.1 vs 789.2±115.9, P < 0.001). Categorized into quartiles, shorter LTL consistently associated with higher HF hospitalization rates in both non-AF (P for trend < 0.001) and AF groups (P for trend = 0.022). Adjusting for age, sex, and cardiovascular risk factors, longer LTL correlated with reduced HF risk (HR, 0.87; 95% CI, 0.77-0.98; P = 0.017), independent of AF presence (P for interaction=0.629). This study establishes an association between shorter LTL and increased HF hospitalization rates, regardless of AF presence. These findings underscore the significance of LTL as a potential prognostic biomarker for HF, emphasizing its relevance in both AF and non-AF populations

Effect of carvedilol versus placebo on cardiac function in anthracycline-exposed survivors of childhood cancer (PREVENT-HF): a randomised, controlled, phase 2b trial

Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness-dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov, NCT027175073, and enrolment and follow-up are complete. Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6-36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378-730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (-0·14 [95% CI -0·43 to 0·16] in the carvedilol group vs -0·45 [-0·77 to -0·13] in the placebo group; difference 0·31 [95% CI -0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities.

Abstract 17586: Physical Activity Associates With a Greater Reduction in Heart Failure Risk Among Individuals With Depression and/or Anxiety

Introduction: Physical activity (PA) has shown a dose-dependent reduction in the incidence of heart failure (HF) by mitigating stress-related neural activity (SNA). Accordingly, we postulated that the impact of PA on HF incidence may be more pronounced in individuals with chronic stress conditions (e.g., depression and/or anxiety) that associate with heightened baseline SNA. Objective: To test whether PA confers a greater reduction in HF incidence among individuals with (vs. without) pre-existing depression and/or anxiety. Methods: Among 48,673 participants (median age 60 years, 40% male) in the Mass General Brigham Biobank, self-reported PA data were collected through a health survey and converted to metabolic equivalent of task minutes per week. Data on incident HF, its subtypes, depression, anxiety, and cardiovascular risk factors were obtained using the International Classification of Disease Codes. Cox regression was employed to assess the association between PA and ten-year HF risk and to examine potential interactions. Results: PA (per each standard deviation) is independently associated with greater reductions in all HF risk among individuals with depression and/or anxiety (standardized hazard ratio [HR] [95% confidence interval (CI)]: 0.735 [0.648, 0.834], p<0.001) compared to those without depression and/or anxiety (0.821 [0.781, 0.864], p<0.001, p-interaction=0.038*). Similar associations were observed between PA and the risk of HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) among those in whom HF could be classified, Fig1. Conclusions: PA is associated with greater reductions in risk of incident HF, including HFpEF and HFrEF, with the greatest reductions in those with pre-existing depression and/or anxiety. These findings highlight the potential for improved cardiovascular benefits linked to PA in individuals with elevated baseline SNA.

Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.

The effects of α and ß adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of α and ß adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF. Genetic variants within the cis regions encoding the adrenergic receptors α1A, α2B, ß1, and ß2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases). Lower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, P = 0.001) and 0.95 (95% CI 0.93-0.97, P = 8 × 10-6). Conversely, lower α2B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, P = 3 × 10-7). No evidence of an effect of lower ß2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, P = 0.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease. This study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.

SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis

The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79–0.95) and of heart failure (RR 0.67; 95% CI 0.61–0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75–1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68–0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72–0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.

Association of Dental Diseases and Oral Hygiene Care With the Risk of Heart Failure in Patients With Type 2 Diabetes: ANationwide Cohort Study.

Background To evaluate the association of dental diseases and oral hygiene care with incidence of heart failure (HF) among patients with type 2 diabetes. Methods and Results This study included 173 927 patients with type 2 diabetes aged ≥40 years, who underwent Korean National Health Insurance Service health examinations in 2008 and were followed up until the end of 2017. Hazard ratios (HRs) and 95% CIs for HF were estimated using multivariable Cox proportional hazards regression analysis. During a median follow-up of 9.3 years, 1.94% of participants developed HF. An increased number of missing teeth was associated with a higher risk of HF (P<0.001). HRs of HF increased among individuals with ≥15 missing teeth (HR, 1.37 [95% CI, 1.14-1.64]) compared with those without missing teeth. Decreased risk of HF was observed in individuals with ≥1 time/year of professional dental cleaning (HR, 0.93 [95% CI, 0.87-0.99]) and in those with ≥2 times/d of toothbrushing (HR, 0.90 [95% CI, 0.82-0.98]) compared with those without these practices. While combined presence of missing teeth and periodontal disease (P=0.004) or dental caries (P=0.007) increased HF risk, combined oral hygiene care was associated with further HF risk reduction (P=0.024). Better oral hygiene care was associated with decreased HF risk, even as the number of missing teeth increased (P<0.001). Conclusions Among patients with type 2 diabetes, dental diseases and oral hygiene care are important determinants of HF development. Dental disease management and good oral care may prevent HF in patients with type 2 diabetes.

Stabilization of kidney function and reduction in heart failure events with sodium-glucose co-transporter 2 inhibitors: A meta-analysis and meta-regression analysis.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) events regardless of diabetes status. However, factors associated with their efficacy in HF reduction remain unknown. This study aims to identify clinically relevant markers for the efficacy of SGLT2 inhibitors in HF risk reduction. We searched PubMed/MEDLINE and EMBASE for randomized placebo-controlled trials of SGLT2 inhibitors reporting a composite of HF hospitalization or cardiovascular death in participants with or without type 2 diabetes published until 28 February 2023. Random-effects meta-analysis and mixed-effects meta-regression were conducted to evaluate the association between the outcomes and clinical variables, including changes in glycated haemoglobin, body weight, systolic blood pressure, haematocrit and overall/chronic estimated glomerular filtration rate (eGFR) slope. Thirteen trials with 90 413 participants were included. SGLT2 inhibitors reduced the hazard ratio of the composite of HF hospitalization or cardiovascular death (hazard ratio 0.77; 95% confidence interval, 0.74-0.81; p < .0001). In meta-regression analysis, chronic eGFR slope (eGFR change after the initial dip) was significantly associated with the composite outcome (p = .017), and each 1 ml/min/1.73 m2 /year improvement in chronic eGFR slope led to a 14% reduction in the composite outcome. By contrast, changes in the other parameters showed no significant associations. Improvement in chronic eGFR slope, which reflects the stabilization of kidney function, is significantly associated with the efficacy of the SGLT2 inhibitor in HF, highlighting the cardiorenal axis role in the beneficial effects on HF. The chronic eGFR slope can be a surrogate marker of the effects of SGLT2 inhibitors on HF reduction.

Impact of type of dialyzable beta-blockers on subsequent risk of mortality in patients receiving dialysis: A systematic review and meta-analysis.

Beta-blockers has been reported to improve all-cause mortality and cardiovascular mortality in patients receiving dialysis, but type of beta-blockers (i.e., high vs. low dialyzable) on patient outcomes remains unknown. This study aimed at assessing the outcomes of patients receiving dialyzable beta-blockers (DBBs) compared to those receiving non-dialyzable beta-blockers (NDBBs). We searched the databases including PubMed, Embase, Cochrane, and ClinicalTrials.gov until 28 February 2022 to identify articles investigating the impact of DBBs/NDBBs among patients with renal failure receiving hemodialysis/peritoneal dialysis (HD/PD). The primary outcome was risks of all-cause mortality, while the secondary outcomes included risk of overall major adverse cardiac event (MACE), acute myocardial infarction (AMI) and heart failure (HF). We rated the certainty of evidence (COE) by Cochrane methods and the GRADE approach. Analysis of four observational studies including 75,193 individuals undergoing dialysis in hospital and community settings after a follow-up from 180 days to six years showed an overall all-cause mortality rate of 11.56% (DBBs and NDBBs: 12.32% and 10.7%, respectively) without significant differences in risks of mortality between the two groups [random effect, aHR 0.91 (95% CI, 0.81-1.02), p = 0.11], overall MACE [OR 1.03 (95% CI, 0.78-1.38), p = 0.82], and AMI [OR 1.02 (95% CI, 0.94-1.1), p = 0.66]. Nevertheless, the pooled odds ratio of HF among patients receiving DBBs was lower than those receiving NDBB [random effect, OR 0.87 (95% CI, 0.82-0.93), p<0.001]. The COE was considered low for overall MACE, AMI and HF, while it was deemed moderate for all-cause mortality. The use of dialyzable and non-dialyzable beta-blockers had no impact on the risk of all-cause mortality, overall MACE, and AMI among dialysis patients. However, DBBs were associated with significant reduction in risk of HF compared with NDBBs. The limited number of available studies warranted further large-scale clinical investigations to support our findings.

Abstract 14412: Statin Use and Incident Heart Failure by Race and Cardiovascular Disease Risk in a Real World Primary Prevention Cohort

Background: Statins are indicated for primary prevention in patients with elevated risk of atherosclerotic CVD (ASCVD). However, statin associated risk reduction in heart failure (HF) is uncertain. There remain racial disparities in statin prescription and associated ASCVD outcomes. We evaluated the association of statin therapy and incident HF stratified by race and estimated ASCVD risk in a primary prevention cohort. Methods: Statin use in Black and White patients without ASCVD and HF was evaluated (2013-2019) based on the ACC/AHA 10y risk groups ( Borderline [5%-7.4%], Intermediate [7.5-19.9%], or High [≥20%]). Guideline Directed Statin Intensity (GDSI) was defined as “at least moderate” for intermediate and high risk patients. Statin use and HF outcome was assessed via electronic health care record and ICD-10 codes. Cox regression models, fully adjusted for CVD risk factors, were used to calculate HRs for the association between statin use and incident HF. Results: In 270,079 patients, 39% Black and 32% White patients were categorized as intermediate or high ASCVD risk. Proportionally fewer Black patients in intermediate (22% vs. 31%) and high (40% vs. 44%) risk groups received "any statin" (all p&lt;0.001). At 6y follow up, incident rate of HF was 12.9 per 1000-person-y in those with highest ASCVD risk. Black patients had higher risk of HF events [(HR HF 1.11 (1.05-1.17), p&lt;0.001)]. In both populations, high risk patients not on any statin had significantly higher risk of HF [(HR HF 1.42 (1.04-1.93) in Black and 1.22(1.08-1.37) in White] ( Table ). The interaction between race and statin use was not a significant predictor of incident HF. Conclusion: In a large healthcare system, statin use was low among White and Black patients. Lack of statin therapy was associated with a higher risk of incident HF amongst those at highest ASCVD risk. Further research is needed to study the role of statins in primary prevention of HF, especially in higher risk populations.

The evolution of “pillars of therapy” to reduce heart failure risk and slow diabetic kidney disease progression

The evolution of therapy to slow chronic kidney disease progression has changed dramatically over the last five years and is anticipated to change even more in the coming two to four years. What was traditionally noted as “renal sparing therapy” with blockers of the renin-angiotensin system (RAS) has now expanded to the use of inhibitors of sodium-glucose transport 2 (SGLT2) agents as well as the nonsteroidal mineralocorticoid receptor blocker, finerenone. These three “pillars of therapy” have slowed kidney disease progression by more than 50% compared to RAS blockers alone. Additionally, finerenone and SGLT2 inhibitors significantly reduce heart failure hospitalizations and the development of heart failure. Moreover, they improve exercise tolerance and reduce the risk of cardiovascular death, even though they do not affect atherosclerotic heart disease development. These data, taken together, demonstrate a “three pillar” therapy approach for cardiorenal risk reduction in people with type 2 diabetes who have any level of kidney disease.

Predicting Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy

Predicting Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy

Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study.

Patients with type 2 diabetes who have cardiovascular disease and are receiving empagliflozin have a lower rate of primary composite cardiovascular outcomes. In contrast, glimepiride increases cardiovascular hospitalization when combined with metformin. Here, we assessed the effects of empagliflozin and glimepiride on endothelial function using flow-mediated dilation (FMD). In this prospective, open-label, randomized, parallel-group study, 63 patients with type 2 diabetes received metformin and insulin glargine U100 for 12 weeks. This was followed by additional treatment with empagliflozin or glimepiride for 12 weeks. The primary outcome was the change in the FMD measurement (ΔFMDs) at 24 weeks of additional treatment. Secondary outcomes comprised changes in metabolic markers and body composition. The empagliflozin group (n = 33) and glimepiride group (n = 30) showed no significant differences in ΔFMDs (empagliflozin, −0.11 [95%CI: -1.02, 0.80]%; glimepiride, −0.34 [95%CI: -1.28, 0.60]%; P = 0.73). Additionally, changes in glycated hemoglobin were similar between the two groups. However, a significant difference in body weight change was observed (empagliflozin, −0.58 [95%CI: -1.60, 0.43] kg; glimepiride, 1.20 [95%CI: 0.15, 2.26] kg; P = 0.02). Moreover, a body composition analysis revealed that body fluid volume significantly decreased after empagliflozin treatment (baseline, 35.8 ± 6.8 L; after 12 weeks, −0.33 ± 0.72 L; P = 0.03). Hence, although empagliflozin did not improve endothelial function compared with glimepiride for patients with type 2 diabetes, it did decrease body fluid volumes. Thus, the coronary-protective effect of empagliflozin is not derived from endothelial function protection, but rather from heart failure risk reduction.Trial registration: This trial was registered on September 13, 2016; UMIN000024001.

The association of walking pace and incident heart failure and subtypes among postmenopausal women.

To investigate the association between walking pace and the risk of heart failure (HF) and HF sub-types. We examined associations of self-reported walking pace with risk of incident HF and HF subtypes of preserved (HFpEF) and reduced (HFrEF) ejection fractions, among 25,183 postmenopausal women, ages 50-79 years. At enrollment into the Women's Health Initiative cohort in 1993-1998, this subset of women was free of HF, cancer, or the inability to walk one block, with self-reported information on walking pace and walking duration. Multivariable Cox regression was used to examine associations of walking pace (casual <2 mph [referent], average 2-3 mph, and fast >3 mph) with incident HF. We also examined the joint association of walking pace and duration with incident HF. There were 1455 incident adjudicated acute decompensated HF hospitalization cases during a median of 16.9 years of follow-up. There was a strong inverse association between walking pace and overall risk of HF (HR=0.73, 95% CI [0.65, 0.83] for average vs. casual walking; HR=0.66, 95%CI [0.56, 0.78] for fast vs. casual walking). There were similar associations of walking pace with HFpEF (HR=0.73, 95%CI [0.62, 0.86] average vs. casual; HR=0.63, 95%CI [0.50, 0.80] for fast vs. casual) and with HFrEF (HR=0.72, 95%CI [0.57, 0.91] for average vs. casual; HR=0.74, 95%CI [0.54, 0.99] for fast vs. casual). The risk of HF associated with fast walking with less than 1h/week walking duration was comparable with the risk of HF among casual and average walkers with more than 2h/week walking duration. Walking pace was inversely associated with risks of overall HF, HFpEF, and HFrEF in postmenopausal women. Whether interventions to increase the walking pace in older adults will reduce HF risk and whether fast pace will compensate for the short duration of walking warrants further study.

High fitness levels attenuate the increased risk of heart failure due to low socioeconomic status: A cohort study

High fitness levels attenuate the increased risk of heart failure due to low socioeconomic status: A cohort study

Epidemiologic Determinants of Dynamics in Heart Failure Prevalence and Mortality in Older U.S. Adults

Recent declines in heart failure (HF) prevalence and increases in mortality among older adults in the US suggest the need for research to investigate the relative contribution of the epidemiological determinants of these two processes to their historical and current trends. Study data were derived from a 5% sample of Medicare beneficiaries, 1991-2017. Partitioning analysis was used to decompose age-adjusted prevalence and incidence-based mortality (IBM) into their constituent components. HF prevalence trend decomposition demonstrated three phases: (a) Decelerated Increasing Prevalence (1994-2006) mainly driven by decreasing incidence, overpowering increasing survival, (b) Accelerated Declining Prevalence (2007-2014) and (c) Decelerated Declining Prevalence (2015-2017), mainly driven by declining incidence, overpowering declining survival. For HF IBM four phases were identified: (a) Decelerated Increasing Mortality (1994-2001) with declining incidence and increasing survival driving deceleration, (b) Accelerated Declining Mortality (2002-2012), (c) Decelerated Declining Mortality (2013-2016), mainly driven by declining incidence, overpowering declining survival, and (d) Accelerated Increasing Mortality (2017) mainly driven by declining survival, overpowering declining incidence. Study findings suggest that the recent decade-long decline in HF prevalence and 15-year decline in HF mortality mainly reflected decreasing incidence, while the most recent increase in mortality was due to declining survival, which may be associated with the Hospital Readmission Reduction Program. If current trends of incidence and survival persist, HF prevalence and mortality are forecasted to grow, suggesting that actions to reduce HF risk factors and improve treatment and management of HF after diagnosis are warranted.