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BACKGROUND: Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study). METHODS: We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (Δage) and classified individuals as having normal, accelerated, or decelerated aging, if Δage was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of Δage, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors. RESULTS: The study population included 9877 FHS participants (mean age, 55±13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9±7 years). After 17±8 years of follow-up, every 10-year increase of Δage was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12–1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17–1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05–1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30–1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14–1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74–0.95]). CONCLUSIONS: ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk. [ABSTRACT FROM AUTHOR]

A novel, comprehensive health risk index for adults has been validated and is now ready for use to improve the health of individuals and populations. This health risk index provides an estimate of the avoidable risk of death for adults 30 years or older. It includes 12 evidence-based clinical and behavioral risk factors and was validated on discrimination and calibration using the NHANES (National Health and Nutrition Examination Survey) and Framingham Heart Study cohorts. The results from both cohorts were consistent and similar. Discrimination was good, and calibration was acceptable but tended to overpredict mortality risk for females in the higher-risk deciles. [ABSTRACT FROM AUTHOR]

Background--Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. Methods and Results--In a cross-sectional analysis, including ≤9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans without known cardiovascular disease and enrolled in the Framingham Heart Study, Coronary Artery Risk Development in Young Adults, Multi-Ethnic Study of Atherosclerosis, and Genetic Epidemiology Network of Arteriopathy studies, we tested a 62 T2D-loci genetic risk score for association with measures of SCA, including coronary artery or abdominal aortic calcium score, common and internal carotid artery intima-media thickness, and ankle-brachial index. We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors-adjusted model (significance, P<0.01=0.05/5, number of traits analyzed). An inverse association with coronary artery calcium score in Multi-Ethnic Study of Atherosclerosis Europeans (fully-adjusted P=0.004) and with common carotid artery intima-media thickness in the Framingham Heart Study (P=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance genetic risk sub-scores in the Framingham Heart Study and in the Coronary Artery Risk Development in Young Adults. Conclusions--SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genomewide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and cardiovascular disease risk loci. [ABSTRACT FROM AUTHOR]

Background: Endogenous sex hormones have been related to cardiovascular outcomes and mortality. We hypothesized that sex hormones are related to atrial fibrillation (AF) in a community-based cohort of middle-aged to older men.Methods and Results: We examined testosterone, estradiol, and dehydroepiandrosterone sulfate in relation to incident AF in men participating in the Framingham Heart Study. We assessed the 10-year risk of AF in multivariable-adjusted hazard models. The cohort consisted of 1251 men (age, 68.0±8.2 years), of whom 275 developed incident AF. We identified a significant interaction between age and testosterone and, therefore, stratified men into age 55 to 69 years (n=786), 70 to 79 years (n=351), and ≥80 years (n=114). In men aged 55 to 69 years, each 1 SD decrease in testosterone was associated with hazard ratio (HR) 1.30 (95% confidence interval [CI], 1.07-1.59) for incident AF. The association between testosterone and 10-year incident AF in men 70 to 79 years did not reach statistical significance. In men≥80 years, a 1 SD decrease in testosterone was associated with HR 3.53 (95% CI, 1.96-6.37) for AF risk. Estradiol was associated with incident AF (HR, 1.12; 95% CI, 1.01-1.26). Dehydroepiandrosterone sulfate had a borderline association with risk of AF that was not statistically significant (HR, 1.12; 95% CI, 0.99-1.28).Conclusions: Testosterone and estradiol are associated with incident AF in a cohort of older men. Testosterone deficiency in men≥80 years is strongly associated with AF risk. The clinical and electrophysiological mechanisms underlying the associations between sex hormones and AF in older men merit continued investigation. [ABSTRACT FROM AUTHOR]

The article discusses a study on a meta-analysis of genome-wide association studies (GWAS) findings for ankle-brachial index (ABI). It hypothesized that some generic variants for ABI would be associated with coronary arterial disease (CAD) while some genetic variants will be associated with peripheral arterial disease (PAD). It suggests the lack of a common variants with large effects on ABI. INSET: CLINICAL PERSPECTIVE.

The article focuses on a study that determined whether persons with greater amounts of periaortic fat are more likely to have clinical peripheral artery disease (PAD) and a low ankle-brachial index. Researchers applied a novel volumetric quantitative approach to measure the periaortic fat surrounding the thoracic aorta in 1205 participants from the Framingham Heart Study Offspring cohort. The results are said to indicate a potential mechanism whereby obesity might lead to the development of PAD.

The article discusses a research study on how the risk of heart failure (HF) among adults with African and European ancestry is associated with genome-side variation. The made use of the meta-analyses under the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium combined results from four studies on each single-nucleotide polymorphism to estimate the overall association and P value. The results have enabled the researchers to identify two loci associated with HF incidents exceeding genome-wide significance.

Background: Biological age (BA) may reflect an individual's aging process better than chronological age (CA). The objective of our study was to construct BA measures from different types of biomarkers and test their associations with mortality and age-related disease in a community-based sample. Methods: We selected 6 clinical predictors that capture pulmonary, vascular, atherosclerosis, insulin sensitivity, inflammatory, and kidney domains of aging, and 9 inflammatory biomarkers measured in Framingham Heart Study Offspring cohort participants at exams 7 (1998-2001, N=3539, mean age 62±10) and 8 (2005-2008, N=3021, mean age 67±9). We used the Klemera-Doubal method to calculate a clinical variable BA and an inflammatory marker BA. We computed BA using DNA methylation (DNAm) data at exam 8 using Horvath's method. For each of the measures we computed the difference (ΔAge) between BA and CA and modeled the effects of ΔAge after accounting for CA. We followed participants through 2014 for all-cause mortality (N=713), cardiovascular disease (CVD, N=412), coronary heart disease (CHD, N=223), stroke (N=129), and cancer (N=509). Results: Inflammatory and clinical ΔAge were correlated (=0.35, =0.33, for exams 7 and 8 respectively), and also across exams (inflammatory ΔAge exam 7 vs 8: =0.61; clinical ΔAge: =0.76). DNAm ΔAge was not significantly correlated with exam 8 inflammatory or clinical ΔAge. After adjusting for CA and sex, larger inflammatory and clinical ΔAge, corresponding to older BA than CA, was associated with significantly increased hazards of all-cause mortality, CVD, and CHD (Table). The clinical and inflammatory ΔAge were significant (p<0.05) in models containing both measures. DNAm ΔAge was associated with increased hazards of all-cause mortality, CVD, cancer, and stroke, and remained significant in a model for mortality that also included inflammatory ΔAge (p<0.05). Conclusions: Our findings suggest the three BA measures may be complementary in predicting risk for age-related disease. [ABSTRACT FROM AUTHOR]

The authors reflect on the study "Propofol Ameliorates Hyperglycemia-Induced Cardiac Hypertrophy and Dysfunction via Heme Oxygenase-1/Signal Transducer and Activator of Transcription 3 Signaling Pathway in Rats," by J. Xu and colleagues. They say that the study show that oxidative stress and myocardial damage increase significantly among type 1 diabetic rats. They add that propofol increases heme oxygenase-1 (HO-1) activity in the heart despite less increase in HO-1 protein expression.

Diabetic cardiomyopathy is a heart disease in diabetic patients, identified as ventricular dysfunction in the absence of coronary artery disease and hypertension. The molecular mechanisms underlying diabetic cardiomyopathy are still poorly understood. The protein and lipid kinase phosphoinositide 3-kinases (PI3Ks) have been suggested to regulate cardiac injury during diabetes. In this review, we will summarize the role of different PI3K isoforms and of their downstream signaling in the pathogenesis of diabetic cardiomyopathy, including the regulation of cardiac metabolism, contractility, hypertrophy, myocardial cell death, and inflammation.