Lower Risk Of Heart Failure Research Articles

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

Control for multiple risk factors and incident heart failure and mortality in patients with diabetes mellitus: insights from the kailuan cohort study

Abstract Purpose This study aimed to evaluate the relationship between control for multiple risk factors and diabetes-related heart failure and all-cause mortality, and to explore the extent to which the excess risk can be reduced. Methods Diabetes participants with pre-existing heart failure documented in discharge register or medical insurance records and incomplete baseline risk factor information were excluded. Each of these patients was then matched randomly to four control subjects. The degree of risk factor control was defined by attainment of target values for blood pressure, body mass index , low-density lipoprotein cholesterol, fasting blood glucose, high-sensitive C-reactive protein and smoking. The primary outcome was newly diagnosed heart failure, and the secondary outcome was all-cause mortality.Fine-Gray and Cox regression were performed to estimate the risk of heart failure and all-cause mortality among diabetes patients in relation to the degree of control for multiple risk factors respectively, and the group with ≤1 risk factor control was set as the reference group. All-cause mortality was used as a competing risk in the Fine-Gray model. Results A total of 17,676 patients with diabetes and 69,493 matched non-diabetic control subjects were included. Of these, 84.2% were men and the mean age was 56.2±10.7 years. Over a median follow-up of 11.2 (13.1-15.0) years, a total of 1,070 cases of heart failure and 4,121 cases of all-cause mortality were identified among patients with diabetes. Significant inverse associations were observed between the number of well-controlled risk factors and the risk of incident adverse outcomes in diabetes patients. For each additional risk factor that was controlled, there was an associated 16% decrease in the risk of heart failure and a 10% decrease in the risk of all-cause mortality. The incidence rate of heart failure among diabetes patients was at its lowest for those with ≥5 risk factors (HR: 0.46, 95% CI: 0.34-0.62), and it constantly increased with a lower number of well-controlled risk factors. As for all-cause mortality, the lowest risk was associated with optimal risk factor control (HR: 0.59, 95% CI: 0.50-0.68). Among diabetes patients with ≥5 risk factors that were well controlled, the adjusted hazard ratio for heart failure and all-cause mortality was 1.25 (95%CI: 0.99-1.56) and 1.17(95%CI: 1.05-1.31) respectively, as compared with controls. The protective impact of comprehensive risk factor control on the risk of heart failure was more pronounced among men than women, as well as among those using antihypertensive medications than non-users. Conclusions Control for multiple risk factors is related to a lower risk of heart failure and all-cause mortality in an accumulative and sex-specific manner. Compared to the general population, patients with diabetes mellitus remains associated with an increased risk for the outcomes in spite of the optimization of risk factor control.

Effect of the Mediterranean diet on incidence of heart failure in European countries: a systematic review and meta-analysis of cohort studies.

Heart failure (HF) is one of the most common cardiovascular disorders, and its prevalence is increased due to age, genetics, and lifestyle factors. Emerging evidence suggests that the Mediterranean Diet (Med Diet) is linked to lower all-cause mortality in patients with increased cardiovascular disease risk, such as those with HF. To conduct a systematic review and meta-analysis of observational studies into the relationship between the Med Diet on HF risk. Several databases (PubMed, Scopus, Web of Science and Cochrane Library) until the 01st of May 2023 were searched. Our research was conducted based on the updated 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were reported as risk ratios (RRs) with their 95% confidence intervals (CIs) as results of multivariate or univariate analyses. From the original 1206 studies collected, six observational prospective studies were included, with a total of 216,385 European participants without evidence of HF at baseline. Over a mean period of 11 years of follow-up, a 1-point increase in the Med Diet score was associated with a significantly lower risk of HF (RR = 0.940; 95% CI: 0.912-0.969, p < 0.0001; I2 = 42.9%). Categorised by sex, a higher adherence to Med Diet was associated with a significantly lower incidence of HF in women (RR = 0.942; 95% CI: 0.912-0.973, p = 0.001; I2 = 41.8%), but not in men. The overall quality of included studies was good. Higher adherence to Med Diet across European countries is associated with lower risk of HF, particularly in women.

Artificial intelligence driven definition of food preference endotypes in UK Biobank volunteers is associated with distinctive health outcomes and blood based metabolomic and proteomic profiles

BackgroundSpecific food preferences can determine an individual’s dietary patterns and therefore, may be associated with certain health risks and benefits.MethodsUsing food preference questionnaire (FPQ) data from a subset comprising over 180,000 UK Biobank participants, we employed Latent Profile Analysis (LPA) approach to identify the main patterns or profiles among participants. blood biochemistry across groups/profiles was compared using the non-parametric Kruskal–Wallis test. We applied the Limma algorithm for differential abundance analysis on 168 metabolites and 2923 proteins, and utilized the Database for Annotation, Visualization and Integrated Discovery (DAVID) to identify enriched biological processes and pathways. Relative risks (RR) were calculated for chronic diseases and mental conditions per group, adjusting for sociodemographic factors.ResultsBased on their food preferences, three profiles were termed: the putative Health-conscious group (low preference for animal-based or sweet foods, and high preference for vegetables and fruits), the Omnivore group (high preference for all foods), and the putative Sweet-tooth group (high preference for sweet foods and sweetened beverages). The Health-conscious group exhibited lower risk of heart failure (RR = 0.86, 95%CI 0.79–0.93) and chronic kidney disease (RR = 0.69, 95%CI 0.65–0.74) compared to the two other groups. The Sweet-tooth group had greater risk of depression (RR = 1.27, 95%CI 1.21–1.34), diabetes (RR = 1.15, 95%CI 1.01–1.31), and stroke (RR = 1.22, 95%CI 1.15–1.31) compared to the other two groups. Cancer (overall) relative risk showed little difference across the Health-conscious, Omnivore, and Sweet-tooth groups with RR of 0.98 (95%CI 0.96–1.01), 1.00 (95%CI 0.98–1.03), and 1.01 (95%CI 0.98–1.04), respectively. The Health-conscious group was associated with lower levels of inflammatory biomarkers (e.g., C-reactive Protein) which are also known to be elevated in those with common metabolic diseases (e.g., cardiovascular disease). Other markers modulated in the Health-conscious group, ketone bodies, insulin-like growth factor-binding protein (IGFBP), and Growth Hormone 1 were more abundant, while leptin was less abundant. Further, the IGFBP pathway, which influences IGF1 activity, may be significantly enhanced by dietary choices.ConclusionsThese observations align with previous findings from studies focusing on weight loss interventions, which include a reduction in leptin levels. Overall, the Health-conscious group, with preference to healthier food options, has better health outcomes, compared to Sweet-tooth and Omnivore groups.Graphical

Cardiovascular Outcomes of Uric Acid Lowering Medications: A Meta-Analysis.

Although hyperuricemia is a recognized risk factor for cardiovascular diseases, mixed results have been reported regarding the associations between uric acid-lowering medications and cardiovascular events. This meta-analysis compared the cardiovascular outcomes of different uric acid-lowering medications and placebo. Following PRISMA guidelines, we searched OVID Medline, Embase, Web of Science, and Cochrane databases to identify potentially relevant articles until December 2023. Studies must be randomized or observational, report cardiovascular and mortality outcomes, and compare uric acid-lowering medications to placebo or each other. Data was analyzed using Revman (version 5.4) software. A total of 3,393 studies were searched, after which 47 studies were included, totaling 3,803,509 patients (28 studies comparing xanthine oxidase inhibitors (XOI) versus placebo, 17 studies comparing allopurinol and febuxostat, and 2 studies comparing XOI and uricosuric agents). Overall mean age was 57.3years, and females comprised 20.8% of all studies. There were no significant differences between XOI and placebo for cardiovascular outcomes (mortality, myocardial infarction, major adverse cardiovascular events, heart failure, or arrhythmia). There was significant heterogeneity in all these pooled analyses. Comparing Allopurinol to Febuxostat, there was a lower risk of heart failure in febuxostat than allopurinol in 3 RCTs (OR 0.66, 95% CI 0.50-0.89, p = 0.006). Other cardiovascular outcomes were not different. Lastly, when comparing XOI and uricosuric agents, no significant differences in MI rates were evident. XOI was not associated with reduced cardiovascular events compared to placebo. When comparing XOI agents, Febuxostat might reduce the risk of HF, but future studies are required to confirm the findings from the current study.

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.

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.

Comprehensive Multiple Risk Factor Control in Type 2 Diabetes to Mitigate Heart Failure Risk: Insights From a Prospective Cohort Study.

The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

Vitamin D and heart failure risk among individuals with type 2 diabetes: observational and Mendelian randomization studies

BackgroundEvidence is limited and inconsistent regarding vitamin D and heart failure (HF) risk in people with type 2 diabetes (T2D), among whom vitamin D insufficiency or deficiency is common. ObjectivesThis study aimed to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with HF risk among individuals with T2D, in observational and Mendelian randomization (MR) frameworks. MethodsObservational analyses were performed among 15,226 T2D participants aged 40–72 y from the UK Biobank. HF incidence was ascertained through electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum 25(OH)D and HF risk among people with T2D. MR analyses were conducted among 11,260 unrelated participants with T2D. A weighted genetic risk score for genetically predicted 25(OH)D concentration was instrumented using 62 confirmed genome-wide variants. ResultsThe mean ± standard deviation of serum 25(OH)D was 43.4 ± 20.4 nmol/L. During a median follow-up of 11.3 y, 836 incident HF events occurred. Serum 25(OH)D was nonlinearly and inversely associated with HF and the decreasing risk tended to plateau at around 50 nmol/L. Comparing those with 25(OH)D <25 nmol/L, the multivariable-adjusted HR (95% CI) was 0.67 (0.54, 0.83) for participants with 25(OH)D of 50.0–74.9 nmol/L and was 0.71 (0.52, 0.98) for 25(OH)D >75 nmol/L. In MR analysis, each 7% increment in genetically predicted 25(OH)D was associated with 36% lower risk of HF among people with T2D (HR: 0.64, 95% CI: 0.41, 0.99). ConclusionsHigher serum 25(OH)D was associated with lower HF risk among individuals with T2D and the MR analysis suggested a potential causal relationship. These findings indicate a role of maintaining adequate vitamin D status in the prevention of HF among individuals with T2D.

Dietary Minerals and Incident Cardiovascular Outcomes among Never-Smokers in a Danish Case-Cohort Study.

Background: Diet is known to impact cardiovascular disease (CVD) risk, but evidence for the essential minerals of magnesium (Mg), calcium (Ca), and potassium (K) is inconsistent. Methods: We conducted a case-cohort study within a non-smoking subgroup of the Danish Diet, Cancer and Health cohort, a prospective study of 50-64-year-olds recruited between 1993-1997. We identified incident heart failure (HF), acute myocardial infarction (AMI) and stroke cases through 2015 with an 1135-member subcohort. We measured the dietary intake of minerals, also known as elements, and calculated a combined dietary intake (CDI) score based on joint Ca, Mg and K intakes (mg/d) from Food Frequency Questionnaires. We estimated adjusted hazard ratios (HRs) with Cox proportional hazard models. Results: Most HRs examining associations between CDI score and CVD were null. However, the third quartile of CDI was associated with a lower risk for heart failure (HR: 0.89; 95% CI: 0.67, 1.17), AMI (HR: 0.79; 95% CI: 0.60, 1.04), and stroke (HR: 0.63; 95% CI: 0.44, 0.88). Conclusions: We did not find consistent evidence to suggest that higher levels of essential minerals are associated with incident HF, AMI, and stroke, though results suggest a potential U-shaped relationship between select minerals and CVD outcomes.

Bariatric metabolic surgery is associated with a lower risk for heart failure versus GLP-1RAs.

Bariatric metabolic surgery is associated with a lower risk for heart failure versus GLP-1RAs.

Sex and age significantly modulate cardiovascular disease presentation in type 2 diabetes: a large population-based cohort study.

We aimed to describe and compare the incidence of the first cardiovascular event and its major subtypes, coronary heart disease (CHD), cerebrovascular disease, heart failure (HF), or peripheral artery disease (PAD), according to age and sex in a population-based cohort of individuals with type 2 diabetes (T2D) from a Mediterranean region. We used linked primary care electronic medical reports, pharmacy-invoicing data, and hospital admission disease registry records from the SIDIAP database, which contains linked data for 74% of the Catalonian population. We selected individuals with T2D aged 30 to 89 years free of cardiovascular disease (CVD). The primary outcome was the first presentation of CVD. The study cohort included 247,751 individuals (48.6% women, 66.8 ± 11.9 years). During a 6.99-year follow-up, the cumulative incidence of the first cardiovascular event was 23.4%. Men were at higher risk for CVD (hazard ratio [HR]: 1.47 95%CI: 1.45-1.50), CHD (HR: 1.52 95%CI: 1.47-1.57), cerebrovascular disease (HR:1.07 95%CI: 1.03-1.10) and PAD (HR: 2.30 95%CI: 2.21-2.39) than women but at a lower risk for HF (HR:0.70 95%CI: 0.68-0.73). CHD and PAD were the most frequent CVD presentations among men (28.1% and 27.5%) and HF (40.1%) in women. CHD predominated among young participants of both sexes, while HF predominated among women older than 65 and men older than 75. In individuals with T2D, the overall risk and the type of first CVD manifestation largely varied by sex and age. This epidemiological evidence should be considered in clinical practice.

Association of High-Density Lipoprotein Parameters and Risk of Heart Failure: A Multicohort Analysis

BackgroundHigh-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease. ObjectivesThe authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes. MethodsParticipants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models. ResultsAmong 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60]). ConclusionsHigher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.

Sex Differences in the Associations of Traditional Risk Factors and Incident Heart Failure Hospitalization: A Prospective Cohort Study of 102 278 Chinese General Adults.

Evidence regarding sex differences in the associations of traditional risk factors with incident heart failure (HF) hospitalization among Chinese general adults is insufficient. This study aimed to evaluate the potential sex differences in the associations of traditional risk factors with HF among Chinese general adults. Data were from a subcohort of the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project. The traditional risk factors were collected at baseline, and the study outcome was HF-related hospitalization identified from the Inpatients Registry. A total of 102 278 participants (mean age, 54.3 years; 39.5% men) without prevalent HF were recruited. A total of 1588 cases of HF-related hospitalization were captured after a median follow-up of 3.52 years. The incidence rates were significantly higher in men (2.1%) than in women (1.2%). However, the observed lower risk of HF in women was significantly attenuated or even vanished when several traditional risk factors were poorly controlled (P for sex-by-risk factors <0.05). The selected 11 risk factors collectively explained 62.5% (95% CI, 55.1-68.8) of population attributable fraction for HF in women, which is much higher than in men (population attributable fraction, 39.6% [95% CI, 28.5-48.9]). Although women had a lower incidence rate of hospitalization for HF than men in this study, the risk for HF increased more remarkably in women than in men when several traditional risk factors were poorly controlled. This study suggests that intensive preventative strategies are immediately needed in China.

PDE5 inhibition mitigates heart failure in hyperlipidemia

PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40–0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials.

Abstract PO1-11-05: Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study

Abstract Background: While studies have shown that breast cancer survivors with healthier diets have a lower risk of non-breast cancer-specific and all-cause mortality after a breast cancer diagnosis, the relationship between diet quality and cardiovascular disease (CVD) among breast cancer survivors is not well characterized. We examined the association between diet quality at the time of breast cancer diagnosis and CVD-related outcomes in the Pathways Study, a prospective cohort of 3,415 women diagnosed with invasive breast cancer. Methods: This analysis included four diet quality indices (DQIs) consistent with healthy eating: 1. Dietary Approaches to Stop Hypertension (DASH), 2. healthy plant-based dietary index (hPDI), 3. 2015 Healthy Eating Index (HEI), 4. American Cancer Society nutrition guidelines (ACS). Each DQI was calculated from food frequency questionnaires (FFQ) at or around the time of breast cancer diagnosis, between 2005 and 2013, with a higher score representing a more healthful dietary pattern. DQI scores were categorized into quartiles with the most concordant diets in the highest quartile and the least concordant diets in the lowest quartile, for each DQI. CVD outcomes were ascertained through December 31, 2021 and included ischemic heart disease, heart failure, cardiomyopathy, stroke/transient ischemic attack, arrhythmia, cardiac arrest, valvular disease, venous thromboembolic disease and CVD-related death. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from proportional hazards regression accounting for clinical and demographic factors. Results: FFQs were completed an average 2.2 (range=0.3-7.6) months after a breast cancer diagnosis, and a total 623 (18.2%) incident CVD events and 340 (10.0%) CVD-related deaths were ascertained over 39,263 person-years of follow-up. Participants in the highest quartile of the DASH DQI had substantially reduced risks of heart failure (HR=0.50, 95% CI 0.31-0.81), arrhythmia (HR=0.76, 95% CI 0.62-0.93), cardiac arrest (HR=0.75, 95% CI 0.60-0.93), valvular disease (HR=0.77, 95% CI 0.62-0.96), venous thromboembolic disease (HR=0.74, 95% CI 0.59-0.92), and a 33% reduced risk of CVD-related death (HR=0.67, 95% CI 0.48-0.95) relative to those in the lowest quartile. Tests for trend across quartiles of the DASH DQI were also statistically significant at a p-value &amp;lt; 0.03. The only notable association found in the other three DQIs was between hPDI and lower risk of heart failure (HR=0.61, 95% CI 0.39-0.95) in women in the highest quartile compared to the lowest quartile (Table 1). Summary: These findings suggest that diets concordant with DASH and hPDI dietary patterns, may be beneficial for preventing CVD and CVD-related death after a breast cancer diagnosis. Table 1. Cox proportional hazard ratios and 95% confidence intervals for quartiles of diet quality indices and CVD events and CVD-related death Citation Format: Isaac Ergas, Janise Roh, Lawrence Kushi, Carlos Iribarren, Mai Nguyen-Huynh, Jamal Rana, Eileen Rillamas-Sun, Cecile Laurant, Valerie Lee, Richard Cheng, Heather Greenlee, Marilyn Kwan. Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-05.

SGLT2 inhibition, plasma proteins, and heart failure: a proteome-wide Mendelian Randomization and colocalization study.

To investigate the causal contributions of Sodium-glucose cotransporter 2 (SGLT2) inhibition on Heart Failure (HF) and identify the circulating proteins that mediate SGLT2 inhibition's effects on HF. Applying a two-sample, two-step Mendelian Randomization (MR) analysis, we aimed to estimate: (1) the causal impact of SGLT2 inhibition on HF; (2) the causal correlation of SGLT2 inhibition on 4,907 circulating proteins; (3) the causal association of SGLT2 inhibition-driven plasma proteins on HF. Genetic variants linked to SGLT2 inhibition derived from the previous studies. The 4,907 circulating proteins were derived from the deCODE study. Genetic links to HF were obtained through the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) consortium. SGLT2 inhibition demonstrated a lower risk of HF (odds ratio [OR] = 0.44, 95% CI [0.26, 0.76], P = 0.003). Among 4,907 circulating proteins, we identified leucine rich repeat transmembrane protein 2 (LRRTM2), which was related to both SGLT2 inhibition and HF. Mediation analysis revealed that the impact of SGLT2 inhibition on HF operates indirectly through LRRTM2 [β = -0.20, 95% CI (-0.39, -0.06), P = 0.02] with a mediation proportion of 24.6%. Colocalization analysis provided support for the connections between LRRTM2 and HF. The study indicated a causative link between SGLT2 inhibition and HF, with plasma LRRTM2 potentially serving as a mediator.

Cardiorenal outcomes and mortality after sodium-glucose cotransporter-2 inhibitor initiation in type 2 diabetes patients with percutaneous coronary intervention history.

To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching. During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.

Sodium-Glucose Cotransporter-2 Inhibitors vs Sulfonylureas for Gout Prevention Among Patients With Type 2 Diabetes Receiving Metformin

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are a revolutionary treatment for type 2 diabetes (T2D) with cardiovascular, kidney, and serum urate-lowering benefits. To compare risk of incident gout and rate of recurrent flares between patients with T2D initiating SGLT2i vs sulfonylurea, most common second-line glucose-lowering therapy, when added to metformin monotherapy. This sequential, propensity score-matched, new-user comparative effectiveness study using target trial emulation framework included adults with T2D receiving metformin monotherapy in a Canadian general population database from January 1, 2014, to June 30, 2022. Initiation of SGLT2i vs sulfonylurea. The primary outcome was incident gout diagnosis, ascertained by emergency department (ED), hospital, outpatient, and medication dispensing records. Secondary outcomes were gout-primary hospitalizations and ED visits and major adverse cardiovascular events (MACE), as well as recurrent flare rates among prevalent gout patients. Heart failure (HF) hospitalization was assessed as positive control outcome and osteoarthritis encounters as negative control. For target trial emulations, we used Cox proportional hazards and Poisson regressions with 1:1 propensity score matching (primary analysis) and overlap weighting (sensitivity analysis). The analysis was conducted from September to December, 2023. Among 34 604 propensity score matched adults with T2D initiating SGLT2i or sulfonylurea (20 816 [60%] male, mean [SD] age, 60 [12.4] years), incidence of gout was lower among SGLT2i initiators (4.27 events per 1000 person-years) than sulfonylurea initiators (6.91 events per 1000 person-years), with a hazard ratio (HR) of 0.62 (95% CI, 0.48-0.80) and a rate difference (RD) of -2.64 (95% CI, -3.99 to -1.29) per 1000 person-years. Associations persisted regardless of sex, age, or baseline diuretic use. SGLT2i use was also associated with fewer recurrent flares among gout patients (rate ratio, 0.67; 95% CI, 0.55-0.82; and RD, -20.9; 95% CI, -31.9 to -10.0 per 1000 person-years). HR and RD for MACE associated with SGLT2i use were 0.87 (95% CI, 0.77-0.98) and -3.58 (95% CI, -6.19 to -0.96) per 1000 person-years. For control outcomes, SGLT2i users had lower risk of HF (HR, 0.53; 95% CI, 0.38-0.76), as expected, with no difference in osteoarthritis (HR, 1.11; 95% CI, 0.94-1.34). Results were similar when applying propensity score overlap weighting. In this population-based cohort study, the gout and cardiovascular benefits associated with SGLT2i in these target trial emulations may guide selection of glucose-lowering therapy in patients with T2D, at risk for or already with gout.

The EAT-Lancet Diet Index, Plasma Proteins, and Risk of Heart Failure in a Population-Based Cohort

BackgroundThe landmark EAT-Lancet Commission proposed that a planetary health diet is comprised mainly of plant-based foods. However, studies examining whether this diet is associated with heart failure (HF) are currently lacking. In addition, the potential proteomics mechanism on the association between diet and HF warrants further elucidation. ObjectivesThis study aims to both examine the association between the EAT-Lancet diet index and risk of HF and identify plasma proteins underlying such an association. MethodsThis prospective cohort study included 23,260 participants. HF cases during the follow-up were identified through the Swedish national register. An EAT-Lancet diet index (score range: 0-42) was created to assess adherence to the EAT-Lancet reference diet. In a subcohort (n = 4,742), fasting plasma proteins were quantified. ResultsDuring a median follow-up of 25.0 years, 1,768 incident HF cases were documented. After adjusting for sociodemographic, lifestyle, diabetes, hypertension, use of lipid-lowering drugs, and body mass index, the HR per 3-point increase of the EAT-Lancet diet index was 0.93 (95% CI: 0.88-0.97). This association was robust in several sensitivity analyses. Among the included 136 plasma proteins, a total of 8 proteins (AM, GDF15, IL-6, TIM, CTSD, CCL20, FS, and FUR) were both inversely associated with the EAT-Lancet diet index and positively associated with risk of HF; the overall proteomic score mediated 9.4% (95% CI: 2.2%-32.1%) of the association. ConclusionsHigher adherence to the EAT-Lancet diet was associated with a lower risk of HF. The identified eight plasma proteins provide information on potential pathways mediating such an association.