Overt Cardiovascular Disease Research Articles

Interleukin 6 in asymptomatic patients with nonsevere aortic valve stenosis: a post-hoc study of the SEAS trial

Abstract Background Inflammation plays a pivotal role in the pathogenesis of aortic valve stenosis (AS) through cytokine-mediated valve calcification. Studies of explanted valves found associations of an elevated pro-inflammatory cytokine, Interleukin 6 (IL-6), with increased postoperative mortality. However, limited knowledge exists regarding the prognostic value of elevated circulating IL-6 in asymptomatic patients with nonsevere AS. Purpose To investigate the hypothesis that elevated plasma IL-6 concentration ≥7 pg/mL (above the upper limit of normal 95th percentile) correlates with more severe AS and a higher risk of adverse outcomes in asymptomatic patients with nonsevere AS. Methods We analyzed data of 1574 asymptomatic patients who had mild-to-moderate AS, preserved systolic and kidney function, no overt cardiovascular diseases, and an event-free follow-up one year after enrollment in the randomized Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. We ascertained the correlation of year-0 and year-1 IL-6 levels with echocardiographic AS severity, defined as moderate-severe AS in the presence of ≥2 measurements at year-0: aortic valve area <1 cm², mean pressure gradient ≥40 mmHg, maximal transaortic velocity ≥4 m/s, and velocity ratio <0.25. Multivariable regression examined correlations between IL-6 at year-0 and clinical variables. Cox proportional hazard models and competing risk analyses examined associations of elevated IL-6 at year-1 and 4-year risk of the primary composite endpoint of major cardiovascular events (MACE) comprising the first event of cardiovascular death, aortic valve replacement, hospitalization with heart failure, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or ischemic stroke. Results At year-0, among 1574 patients with a mean (SD) age of 67.5 (9.7) years, 629 (40.0%) were women, 263 (16.7%) had moderate-severe AS, and 194 (12.3%) had elevated IL-6. The median relative IL-6 change from year-0 to year-1 was 1.0 (IQR, 0.8-1.4) across AS-severity groups (P=0.12) (Figure 1). In adjusted models, IL-6 at year-0 did not correlate with AS-severity (P=0.30). In mild AS, an elevated IL-6 at year-1 was associated with an increased 4-year MACE risk (HR 1.40; 95% CI, 1.02-1.92; p=0.04) in adjusted Cox regression analyses (Figure 2A). In sensitivity analyses, the annual IL-6 increase >50% combined with normal IL-6 was associated with an increased 4-year MACE-risk of HR 1.48 (95% CI, 1.10-2.00; P=0.009) in patients with mild AS and 1.82 (95% CI, 0.68-1.74; P=0.73) in patients with moderate-severe AS (all P for interaction>0.25) (Figure 2C-D). Conclusion In asymptomatic patients with nonsevere AS, circulating IL-6 remains stable within the reference range in 7 out of 8 patients during a 1-year follow-up, regardless of AS severity. An elevated IL-6 was associated with a 1.4-fold increased 4-year MACE-risk in patients with mild AS, suggesting its possible role as an early risk marker.Figure 1Figure 2

Telomere shortening and cardiac alterations in asymptomatic type 2 diabetes patients: impact of sex

Abstract Background Telomere shortening is associated with the occurrence of deleterious events in the context of cardiometabolic disorders, including type 2 diabetes mellitus (T2DM). However, no evidence is available on the link between leukocyte telomere length (LTL) and subclinical cardiac alterations in T2DM patients. Purpose Our aim is to evaluate the relation between LTL and cardiovascular function in asymptomatic T2DM patients, taking into consideration the impact of the sex. Methods We analyzed a cohort of asymptomatic T2DM patients free from any overt cardiovascular disease (including coronary artery disease) and other T2DM comorbidities. A detailed metabolic and echocardiographic evaluation was performed together with LTL measurements at inclusion and after 2 years of follow-up. Univariate analyses in regard of the comparison of three graded LTL tertiles and different gender were used to test individual relationships betweenbioclinical and echocardiographic parameters and LTL measures. Subsequently, an unsupervised clustering method (self-organizing maps [SOM]) was used to identify cluster at risk of cardiomyopathy. Results We studied 89 T2DM patients aged 50±4 years (43% female) with a mean T2DM duration of 10±5.8 years and an average follow-up of 2.1±0.2 years. Leukocyte TL analysis demonstrated a slight but significant attrition after 2 years. The analysis of echocardiographic variables (transmitral flow velocities, velocity of mitral annular motion, left ventricular ejection fraction) did not show any evidence for ouvert cardiomyopathy. However, in the lower LTL tertile a higher proportion of patients with global longitudinal strain [GLS]<18% was found [41.6% vs. 22.8% vs. 21.6%]. Interestingly, leukocyte TL was associated with T2DM duration, FIB-4, a noninvasive indice used to assess fibrosis associated with non-alcoholic fatty liver disease (NAFLD), and usage of GLP-1 agonists. Comparison of men and women by univariate analysis did not show any differences in both LTL and echocardiographic parameters. However, unsupervised cluster method (SOM) unmasked a subgroup of female T2DM patients with diastolic alterations (e’ mean) and systolic alteration (GLS) both linked with lower LTL, whereas no specific subgroup in male T2DM patients could be distinguished. Conclusion Our study identifies subclinical diastolic and systolic dysfunction together with shorter LTL in a subgroup of female T2DM patients. These findings raise the importance of considering sex effect in the understanding of diabetic cardiomyopathy.

A direct comparison of non-invasive blood markers of liver fibrosis as associates of cardiovascular risk. The Athens cardiometabolic registry

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). This risk increases further with advanced liver fibrosis. To date, non-invasive tests (NIT) for liver fibrosis risk have not been established as diagnostic or prognostic biomarkers of CVD. Purpose The purpose of the study was to compare NIT of liver fibrosis with respect to their associations with vascular injury and cardiovascular (CV) events. Methods Individuals without clinically overt CVD and patients with CVD (total n=1,692), consecutively recruited in the Athens Cardiometabolic Registry, were analysed in this study. We retrospectively evaluated the association of NIT (i.e. Fibrosis-4 index (FIB-4), NAFLD Fibrosis score (NFS), BARD score) with indices of subclinical arterial injury (i.e. carotid wall thickness and atherosclerotic plaque for subclinical atherosclerosis, pulse wave velocity (PWV), for arterial stiffness) and the incidence of CV events. Patients were followed-up for CV events for a median time of 39 months. Results Elevated FIB-4 (>2.67) was associated with vascular damage [adjusted odds ratio (aOR)=2.97, 95% confidence intervals (CI)= 1.71-5.78 for maximal wall thickness (maxWT) and aOR=4.58, 95% CI=2.44-8.60 for PWV] across the entire study population, including those with or without clinically overt CVD. NFS> 0.675 showed similar associations but lacked significant correlation with arterial stiffness in coronary artery disease patients. FIB-4> 2.67 and BARD> 2 were associated with increased risk of the composite endpoint of CV death, acute myocardial infarction, or coronary revascularization [adjusted hazard ratio, (aHR)=2.00, 95% CI= 1.12-3.55 and aHR=3.36, 95% CI=1.03-11.0 for FIB-4 (n=842) and BARD (n=887) respectively]. FIB-4 and BARD as continuous variables confered incremental prognostic value compared to European Systematic Coronary Risk Evaluation 2 (SCORE2). Conclusion In a population with a wide range of cardiometabolic risk, FIB-4 was associated with both markers of atherosclerotic disease and arterial stiffness as well as with adverse CV events. These data support further investigation of FIB-4 as a biomarker of CV risk.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and MACE in patients with established CVD. The clinical value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the clinical value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease (heart failure, coronary artery disease, MASLD, chronic kidney disease). The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels (OR: 1.004, 95% CI:1.000-1.009, P=0.049) and increased triglyceride levels (OR: 1.007, 95%CI: 1.001-1.012, P=0.033) after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score<2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Unseen threat: how subclinical atherosclerosis increases mortality risk in patients with type 1 diabetes

BackgroundCardiovascular disease (CVD), particularly ischemic heart disease, remains the leading cause of death and morbidity in patients with type 1 diabetes. Detecting subclinical atherosclerosis could enhance cardiovascular risk stratification and enable individualised therapies. The aim of this study is to investigate the prevalence and predictors of subclinical atherosclerosis in patients with type 1 diabetes without overt cardiovascular disease (CVD) and to assess its impact on patient survival over a follow-up period of at least 5 years.MethodsThis observational study included 507 patients treated at the Diabetes Unit of the Hospital of Girona Doctor Josep Trueta between 2015 and 2023. The inclusion criteria for patients were as follows: those aged 18 and older with diabetes for a minimum of 10 years or those aged 40 and older with a diabetes for at least 5 years. Subclinical atherosclerosis was identified via ultrasound imaging of the carotid and femoral arteries. Clinical and biochemical evaluations were also conducted. Major cardiovascular events (MACE) and deaths from other causes were monitored, and survival analysis was performed using Kaplan‒Meier methods.ResultsSubclinical atherosclerosis was detected in 218 patients (43%). Multivariate analysis revealed that the male sex, diabetic nephropathy, tobacco exposure, higher HbA1c levels, older age, and longer diabetes duration were significant predictors. During a mean follow-up of 70.64 ± 27.08 months, 19 patients experienced MACE, and 13 died from any cause. The probability of MACE or death was greater in patients with subclinical atherosclerosis, with a hazard ratio (HR) of 25.1 (95% CI 5.81–108, p < 0.001) for MACE and an odds ratio (OR) of 7.57 (95% CI 1.97–53.9, p = 0.004) for death.ConclusionSubclinical atherosclerosis is independently associated with increased overall mortality and MACE in patients with type 1 diabetes. Identifying clinical predictors can improve risk stratification and personalised therapeutic strategies to prevent MACEs in this high-risk population.Graphical

Cardiac events among a cohort of 17,389 patients receiving cancer chemotherapy: short and long term implications

BackgroundThe association between cardiovascular disease and carcinogenesis is bidirectional and well-established. Furthermore, cancer treatment improves overall patient survival, potentially at the cost of incremental and fatal cardiovascular disease (CVD).AimTo evaluate (a) In a real-world cohort, the proportion of patients offered cancer chemotherapy who have antecedent CVD (CVDA); (b) The rates of patient admission with subsequent development of CVD (CVDS) requiring hospital admission post assignment to chemotherapy; (c) The impact of CVDA and CVDS on mortality rates relative to those seen in patients without overt CVD (CVD−) and (d) The time course of mortality in CVD− versus CVDS patients.MethodsRetrospective analysis was performed in deidentified linked health data sets. Correlates of mortality were evaluated by Cox proportional hazards evaluation. Relative and absolute time-variability of CVD as a primary cause of death were determined.ResultsOf the total 17,389 patients, there were 2,159 with CVDA. Over a median follow-up time of 4.6 years, CVDS admissions (n = 8,529) occurred more commonly in the presence of CVDA (70.0% vs. 46.1%, p < 0.001), and more than 50% of CVDS cases occurred in the first 12 months of follow-up. The 5-year mortality rates were 71.5% for CVDA, 64.7% for CVDS, and 40.8% for CVD− (p < 0.001). Development of CVDS was associated with a substantially increased risk of mortality in the next 12 months. The development of CVDs was also associated with an increased risk of cardiovascular, as against non-cardiovascular, mortality (7.1% vs. 1.6%, p < 0.001).ConclusionsApproximately 50% of patients assigned to cancer chemotherapy developed CVDS, heralding a particularly high risk of mortality over the next 12 months. Both CVDA and CVDS are associated with substantial increases in mortality rates relative to those in CVD− patients. This increased risk merits close individual monitoring.

Reference equations for pulse wave velocity, augmentation index, amplitude of forward and backward wave in a European general adult population

Pulsatile hemodynamics have been shown to be independent predictors of cardiovascular events. The aim of the current study was to describe four pulsatile hemodynamic markers in a large, well-established, population-based cohort and to provide reference equations for sex- and age-based standardization of these measurements. 6828 adult participants from the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort study, who were free from overt cardiovascular disease, non-diabetic based on blood test results, and had no history of pharmacological treatment for hypertension, dyslipidemia, and diabetes, comprised the “reference population”. Carotid-femoral pulse wave velocity (cfPWV), augmentation index (AIx), amplitude of forward wave (Pf), and backward wave (Pb) were described in different age categories for both sexes. Sex-specific reference equations for cfPWV, AIx, Pf, and Pb with age as the predictive variable were created using the Lambda-Mu-Sigma (LMS) method. All four parameters increased with age. CfPWV and Pf were higher in males than females, especially in young and middle-age groups (P < 0.001). AIx was higher in females than males in all age categories (P < 0.001). Pb was also higher in females than males in age groups older than 40 years (P < 0.01). Reference equations for the skewness (Lambda), median (Mu), and coefficient of variation (Sigma) values were determined, enabling the calculation of sex- and age-standardized values (z-scores) for each individual’s pulsatile hemodynamic measurement, and an online application was developed. Reference equations derived from a large population-based dataset constitute a suitable tool for the standardization of pulsatile hemodynamics and for the accurate interpretation of vascular aging.

Influence of Sex and Other Risk Factors, Including Kidney Function, on Myocardial Microvascular Function in Individuals with Type 2 Diabetes Free of Overt Cardiovascular Disease: The DiaHeart Study

Influence of Sex and Other Risk Factors, Including Kidney Function, on Myocardial Microvascular Function in Individuals with Type 2 Diabetes Free of Overt Cardiovascular Disease: The DiaHeart Study

NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study.

Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized. Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest. Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th-75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50-157 ng/L), 9 ng/L (6-12 ng/L), and 2.6 ng/L (1.9-3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all P>0.05). Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors.AQ.

Subclinical impairment of the left atrium is associated with MRI-based lung volume but not with parameters from pulmonary function testing

Left atrial (LA) physiology and hemodynamics are intimately connected to cardiac and lung function in health and disease. This study examined the relationship between MRI-based left atrial (LA) size and function with MRI-based lung volume and pulmonary function testing (PFT) parameters in the population-based KORA study cohort of 400 participants without overt cardiovascular disease. MRI quantification assessed LA size/function in sequences with and without ECG synchronization, alongside lung volume. Regression analysis explored the relationship of LA with MRI lung volume and PFT parameters. Among 378 participants (average age 56.3 ± 9.2 years; 42.3% women), non-gated LA size averaged 16.8 cm2, while maximal and minimal LA size from gated measurements were 19.6 cm2 and 11.9 cm2 respectively. The average MRI-derived lung volume was 4.0 L, with PFT showing a total lung capacity of 6.2 L, residual lung volume of 2.1 L, and forced vital capacity of 4.1 L. Multivariate regression analysis, adjusted for age, gender, and cardiovascular risk factors, revealed an inverse association between maximum LA size, non-gated LA, and LA area fraction with lung volume (ß = − 0.03, p = 0.006; ß = − 0.03, p = 0.021; ß = − 0.01, p = 0.012), with no significant association with PFT parameters. This suggests that MRI-based assessment may offer greater sensitivity in detecting subclinical LA impairment than PFT.

Association of aortic diameters and mortality in the general population-an MRI-based study.

Increased diameters of the aorta are associated with increased mortality risk. In the present analyses, we assessed whether aortic diameters are associated with cardiovascular and all-cause mortality in community-dwelling individuals free of known cardiovascular disease (CVD). MRI-derived vascular parameters of the thoracic and abdominal aorta from 2668 participants (median age = 53 years; 51.1% women) of the population-based SHIP-START-2 and SHIP-TREND-0 cohorts without CVD were analyzed. Age- and sex-adjusted, as well as multivariable-adjusted Cox-proportional hazard models, were used to estimate associations of diameters of six different aortic segments to mortality. Over a median follow-up time of 10.6 years (IQR: 8.7; 12.4), a total of 188 participants (126 men and 62 women) died, of which 38 deaths were due to CVD. In unadjusted models, mortality rates were higher in participants with aortic diameters above the median compared to below the median for all investigated aortic sections (all log-rank p < 0.001). In multivariable-adjusted models, the diameters of the ascending thoracic aorta (HR = 1.34 95% CI: 1.04; 1.72, p = 0.022) and of the infrarenal aorta (HR = 3.75 95% CI: 1.06; 13.3, p = 0.040), modeled continuously, were associated with greater cardiovascular mortality. The diameter of the subphrenic aorta was associated with higher cardiovascular mortality only in the age and sex-adjusted model (HR = 3.65 95% CI: 1.01; 13.3, p = 0.049). None of the investigated aortic segments were associated with all-cause mortality. Non-indexed diameters of the ascending thoracic and infrarenal aorta were associated with higher cardiovascular mortality but not with all-cause mortality in a population sample free of clinically overt CVD at baseline. Increased aortic diameter is associated with cardiovascular mortality and can help to identify high-risk patients. Increased aortic diameter is associated with mortality. Non-indexed diameters of the ascending and infrarenal aorta are associated with cardiovascular mortality but not all-cause mortality. Aortic diameter measurements support the estimate of cardiovascular mortality.

The relationship of visceral adiposity with endothelial functions and subclinical atherosclerosis in obese individuals.

On the cardiovascular system, obesity accelerates atherosclerosis progression, inducing pathophysiological changes that are detectable already from young adults. Endothelial dysfunction is one of the earliest vascular alterations observed in obesity. In this study, we aimed to determine endothelial functions and carotid intima-media thickness in patients with obesity without overt cardiovascular disease. The study was conducted with 112 individuals with obesity without overt cardiovascular disease and any chronical diseases (BMI>30 kg/m2) (84 female, 28 male, mean age: 46.3±11.2 years) and 49 healthy individuals with no diseases (33 female, 16 male, mean age: 44.6±10.2 years). All patients were examined for endothelial functions by the flow-mediated dilatation (FMD) method and carotid intima-media thicknesses (CIMT). All measurements were performed by the same imaging specialist, averaging 3 different measurements. In addition to the body mass index and waist circumference visceral adiposity index (VAI) and triponderal mass index (TPI) also calculated. The percentage of FMD obtained by brachial artery ultrasound was significantly lower, visceral adipose tissue, perirenal adipose tissue thicknesses measured by abdominal ultrasound and CIMT were significantly thicker in Group 1 compared to Group 2. FMD had a negative significant correlation with body mass index, visceral adipose tissue thickness, perirenal adipose tissue thickness, and waist and hip circumferences, and carotid intima-media thickness and CIMT had a significant correlation with visceral adipose tissue thickness, perirenal adipose tissue thickness, VAI, TPI and waist, hip circumferences. Individuals with obesity have impaired endothelial functions and greater carotid intima-media thicknesses compared to healthy individuals. This impairment in endothelial functions is proportional to the amount of visceral and perirenal fat accumulation. Parameterss reflecting visceral fat distribution such as VAI and TPI are also related with these impairment.

Low-Dose Aspirin and Progression of Age-Related Hearing Loss

Age-related hearing loss is common in an aging population, affecting communication and contributing to a worsened quality of life. It occurs as a result of cochlear degeneration and may be further exacerbated by inflammation and microvascular changes, as observed in animal models. To compare the effect of daily low-dose aspirin vs placebo on the progression of age-related hearing loss in healthy older adults. A prespecified secondary analysis was conducted of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial. Participants were 279 healthy community-dwelling individuals living in Australia who were aged 70 years or older and free of overt cardiovascular diseases, dementia, and life-limiting illnesses. Participants were recruited between January 1, 2010, and December 31, 2014, and followed up over 3 years. Statistical analysis was completed from June to December 2023. A 100-mg daily dose of enteric-coated aspirin or matching placebo. Hearing measures were air conduction audiometry and binaural speech perception in noise. Assessments were conducted at baseline, 18 months, and 3 years. The change from baseline hearing measures were analyzed using an intention to treat approach. Aspirin and placebo were compared using mixed linear regression models adjusting for age, sex, diabetes, and smoking. Of 279 participants, 154 (55%) were male, and the median age at baseline was 73.1 years (IQR, 71.5-76.2 years). A total of 98 of 138 participants (71%) in the aspirin group and 94 of 141 participants (67%) in the placebo group reported experiencing hearing loss at baseline. Compared with placebo, aspirin did not affect the changes in mean (SD) 4-frequency average hearing threshold from baseline to year 3 (aspirin: baseline, 27.8 [13.3] dB; year 3, 30.7 [13.7] dB; difference, 3.3 [3.9] dB; placebo: baseline, 27.5 [12.6] dB; year 3, 30.9 [13.8] dB; difference, 3.0 [4.8] dB; P = .55) nor any other tested frequencies. An increase in air conduction threshold indicates a deterioration in hearing. Similarly, for the mean (SD) speech reception threshold, there was no significant difference observed between the aspirin and placebo group at the year 3 follow-up assessment (aspirin: baseline, -9.9 [3.8] dB; year 3, -9.1 [3.8] dB; difference, 0.9 [2.9] dB; placebo: baseline, -10.5 [7.1] dB; year 3, -9.6 [4.1] dB; difference, 0.9 [5.9] dB; P = .86). The findings were consistent across sex, age groups, diabetic and smoking status. In this secondary analysis of the ASPREE randomized clinical trial, low-dose aspirin did not affect the progression of age-related hearing loss. More investigation is warranted on whether a longer follow-up or the use of a more powerful anti-inflammatory agent might prove beneficial. anzctr.org.au Identifier: ACTRN12614000496617.

Impairment in Right Ventricular-Pulmonary Arterial Coupling in Overweight and Obesity.

Background: The association of obesity with right ventricular function and the interplay between right heart and pulmonary circulation is incompletely understood. We evaluate the role of obesity as a determinant of right ventricular-pulmonary artery coupling (RVAC). Methods: We retrospectively studied consecutive subjects without overt cardiovascular or pulmonary disease. Subjects were stratified according to body mass index (BMI) as normal weight, overweight, or obese. A transthoracic echocardiographic study was used to assess left and right heart functional and structural parameters. RVAC was assessed using the ratio of peak systolic velocity of the tricuspid annulus to pulmonary artery systolic pressure (PASP). Results: A total of 145 subjects were enrolled with diabetes mellitus incidence higher in obese. There was no difference in left ventricular global longitudinal strain and in PASP or markers of right ventricular systolic function based on BMI. RVAC was significantly lower in the presence of obesity (normal weight: 0.52 (0.19) cm·(sec·mmHg)-1 vs. overweight: 0.47 (0.16) cm·(sec·mmHg)-1 vs. obese: 0.43 (0.14) cm·(sec·mmHg)-1, p = 0.03), even after adjustment for confounders (β: -0.085, 95% confidence interval: -0.163, -0.009, p = 0.029). Conclusions: Our findings highlight the relationship between metabolic impairment and RVAC, suggesting additional mechanisms for heart failure development observed in obese subjects.

Forecasting the Economic Burden of Cardiovascular Disease and Stroke in the United States Through 2050: A Presidential Advisory From the American Heart Association.

Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment. We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions. One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations. The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Funding Acknowledgements None. Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and major adverse cardiovascular events in patients with established CVD. The value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease. The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components (prediabetes, low HDL-C levels, high triglyceride levels, increased waist circumference and high-risk for MASLD) after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels and increased triglyceride levels after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score&amp;lt;2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio (OR:1.017, 95% CI: 1.006-1.028, P=0.003) and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Physical Activity and Progression of Coronary Artery Calcification in Men and Women

ImportancePrior cross-sectional studies have suggested that very high levels of physical activity (PA) are associated with a higher prevalence of coronary artery calcium (CAC). However, less is known regarding the association between high-volume PA and progression of CAC over time.ObjectiveTo explore the association between PA (measured at baseline and during follow-up) and the progression of CAC over time.Design, Setting, and ParticipantsThis cohort study included data from 8771 apparently healthy men and women 40 years and older who had multiple preventive medicine visits at the Cooper Clinic (Dallas, Texas), with a mean (SD) follow-up time of 7.8 (4.7) years between the first and last clinic visit. Participants with reported PA and CAC measurements at each visit during 1998 to 2019 were included in the study. Data were analyzed from March 2023 to February 2024.ExposuresPA reported at baseline and follow-up, examined continuously per 500 metabolic equivalent of task minutes per week (MET-min/wk) and categorically: less than 1500, 1500 to 2999, 3000 or more MET-min/wk.Main Outcomes and MeasuresNegative binomial regression was used to estimate the rate of mean CAC progression between visits, with potential modification by PA volume, calculated as the mean of PA at baseline and follow-up. In addition, proportional hazards regression was used to estimate hazard ratios for baseline PA as a predictor of CAC progression to 100 or more Agatston units (AU).ResultsAmong 8771 participants, the mean (SD) age at baseline was 50.2 (7.3) years for men and 51.1 (7.3) years for women. The rate of mean CAC progression per year from baseline was 28.5% in men and 32.1% in women, independent of mean PA during the same time period. That is, the difference in the rate of CAC progression per year was 0.0% per 500 MET-min/wk for men and women (men: 95% CI, −0.1% to 0.1%; women: 95% CI, −0.4% to 0.5%). Moreover, baseline PA was not associated with CAC progression to a clinically meaningful threshold of 100 AU or more over the follow-up period. The hazard ratio for a baseline PA value of 3000 or more MET-min/wk vs less than 1500 MET-min/wk to cross this threshold was 0.84 (95% CI, 0.66 to 1.08) in men and 1.16 (95% CI, 0.57 to 2.35) in women.Conclusions and RelevanceThis study found that PA volume was not associated with progression of CAC in a large cohort of healthy men and women who were initially free of overt cardiovascular disease.

Carotid Plaques and Hypertension as Risk Factors for Cardiovascular Disease and All-Cause Mortality in Middle-Aged Adults.

Background/Objectives: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. We aim to investigate the synergistic effects of hypertension and carotid plaques on cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology Department of Vilnius University Hospital Santaros Klinikos between 2012 and 2021. The study recruited participants aged 40-65 who did not have overt cardiovascular disease (CVD) and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. Results: The participants were monitored for 4-10 years for CVD events and all-cause mortality. Among 6138 participants, 954 (16%) experienced CVD events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events or all-cause mortality. Conclusions: The risk of CVD events or all-cause mortality was not significantly increased by the combination of hypertension and carotid plaque. Cardiovascular events depend on the extent of atherosclerosis in the carotid arteries.

P-wave alternans rebound following pulmonary vein isolation predicts atrial arrhythmia recurrence.

Numerous P-wave indices have been explored as biomarkers to assess atrial fibrillation (AF) risk and the impact of therapy with variable success. We investigated the utility of P-wave alternans (PWA) to track the effects of pulmonary vein isolation (PVI) and to predict atrial arrhythmia recurrence. This medical records study included patients who underwent PVI for AF ablation at our institution, along with 20 control subjects without AF or overt cardiovascular disease. PWA was assessed using novel artificial intelligence-enabled modified moving average (AI-MMA) algorithms. PWA was monitored from the 12-lead ECG at ~1 h before and ~16 h after PVI (n = 45) and at the 4- to 17-week clinically indicated follow-up visit (n = 30). The arrhythmia follow-up period was 955 ± 112 days. PVI acutely reduced PWA by 48%-63% (p < .05) to control ranges in leads II, III, aVF, the leads with the greatest sensitivity in monitoring PWA. Pre-ablation PWA was ~6 µV and decreased to ~3 µV following ablation. Patients who exhibited a rebound in PWA to pre-ablation levels at 4- to 17-week follow-up (p < .01) experienced recurrent atrial arrhythmias, whereas patients whose PWA remained reduced (p = .85) did not, resulting in a significant difference (p < .001) at follow-up. The AUC for PWA's prediction of first recurrence of atrial arrhythmia was 0.81 (p < .01) with 88% sensitivity and 82% specificity. Kaplan-Meier analysis estimated atrial arrhythmia-free survival (p < .01) with an adjusted hazard ratio of 3.4 (95% CI: 1.47-5.24, p < .02). A rebound in PWA to pre-ablation levels detected by AI-MMA in the 12-lead ECG at standard clinical follow-up predicts atrial arrhythmia recurrence.

Abstract PO4-12-07: INSTITUTIONAL EXPERIENCE IN PATIENTS WITH EARLY BREAST CANCER WHO RECEIVED CARDIOTOXIC THERAPY IN CARDIONCOLOGY UNIT

Abstract Introduction: Early breast cancer (eBC) is the most frequent malignancy diagnosed in women worldwide; fortunately, survival is increasing related to early diagnosis and the incorporation of new drugs. In this scenario, preventing long-term toxicities become essential. Cardiac adverse events related to anthracyclines or trastuzumab such as reduction in left ventricular (LV) systolic function and clinical heart failure (HF), are well known and are the leading cause of morbidity in breast cancer survivors. Cardioprotective strategies and early diagnoses of asymptomatic cardiac dysfunction are essential to optimized management and prevention of overt cardiovascular (CV) disease. We made a specific cardiac assessment within an Oncocardiology multidisciplinary Unit in patients receiving anticancer therapies. We present the experience in patients with eBC treated with anthracyclines, trastuzumab or both in the past five years. Materials and Methods: We conducted an institutional, interventional, prospective study in patients who received anthracyclines, trastuzumab or both according to the standard of care (SoC) in eBC. Basal CV risk stratification included lipid profile, glycated haemoglobin, high-sensitive troponin T (hs-TnT) and N-terminal ProB-type natriuretic peptide (NT-ProBNP) was done. Image assessment was done by echocardiogram (echo), including myocardial deformation assessed by speckle tracking (STRAIN). Follow-up was done according to anthracycline or trastuzumab therapy with echo and cardiac biomarkers during the systemic therapy and at the end of anticancer treatment, 1, 2 and 5 years after. Patients with uncontrolled CV risks factors according to local protocol, asymptomatic cardiac dysfunction defined as decreased strain (&amp;gt;15% compared with baseline) or increased cardiac biomarkers (Hs-TnT &amp;gt;14 at baseline or x3 basal value during the follow-up; NT-ProBNP &amp;gt; 300 in patients with &amp;lt; 50y; &amp;gt; 600 in patients between 50-75-y or &amp;gt;900 in patients &amp;gt; 75 years or older) or patients who develop heart failure during the treatment or follow-up were referred to cardiologist. Results: between 2018 and 2022, 1125 patients were diagnosed with eBC in our institution, and 435 patients received systemic treatment with anthracyclines, trastuzumab or both. During the study period, 165 of these patients were referred to the cardio-oncologist. 60% received treatment with anthracyclines, 36% with trastuzumab and 4.1% with both. The median age was 58(±23.2), 60% had previous CV risk factors. The main reason to refer patients to the cardio-oncologist was asymptomatic cardiac dysfunction and uncontrolled CV risk factors. (Table 1). 60% of patients initiated angiotensin-converting-enzyme inhibitors or Beta-blockers, and only two patients stopped anticancer therapy due to severe cardiac dysfunction. The period of high risk of developing cardiotoxicity was the first year after the end of treatment. Conclusion: multidisciplinary evaluation within a cardio-oncology unit is useful to optimize CV risk factors and to detect asymptomatic cardiac dysfunction in patients receiving cardiotoxic drugs. Table 1. Main reasons to refer patients to cardiologist. Citation Format: Tamara Martos, Laia Carla Belarte-Tornero, Mireia Ble, Eva Gimeno, Laura Sanhauja, Felicidad Martines-Medina, Maria Martinez-García, Maria Castro-Henriques, Joan Albanell, Sonia Servitja. INSTITUTIONAL EXPERIENCE IN PATIENTS WITH EARLY BREAST CANCER WHO RECEIVED CARDIOTOXIC THERAPY IN CARDIONCOLOGY UNIT [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 PO4-12-07.