Journal of the American Heart Association最新文献

Background: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

Methods and results: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ² or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) in transforming growth factor-β pathway genes. The combination of MR and MVP was associated with mitral surgery and arrhythmias. In the subgroup with available images, MAD was enriched in SMAD3 PV compared with other transforming growth factor-β PV (prevalence ratio 1.8 [1.1-2.8], P <0.02). Severe disjunction (>10 mm) was only observed in the transforming growth factor-β subgroup and was further enriched in participants with SMAD3 PV (prevalence ratio 3.1 [1.1-8.6]). MVP (prevalence ratio 5.2 [3.0-9.0]) and MR (PR 2.7 [1.8-3.9]) were increased in participants with MAD, but MAD was not independently associated with adverse cardiac or aortic events.

Conclusions: Pathological mitral valve phenotypes are more prevalent in individuals with PV in transforming growth factor-β pathway genes, particularly SMAD3. MR and MVP but not MAD are associated with adverse aortic and cardiac events. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for heritable thoracic aortic disease should be considered for such individuals, especially if they also have a family history of heritable thoracic aortic disease.

Background: Immigrants are disproportionately affected by cardiovascular disease burden. Heart health screenings, including blood pressure, fasting blood glucose (FBG), and blood cholesterol screenings, can help identify cardiovascular disease risk. Evidence on heart health screenings among diverse immigrant groups is still limited. This study examined the disparities in heart health screenings among the immigrant population compared with US-born White adults.

Methods and results: A cross-sectional design was used to analyze data from the 2011 to 2018 National Health Interview Survey. Generalized linear models with Poisson distribution were applied to compare the prevalence of annual blood pressure, fasting blood glucose, and blood cholesterol screenings among Latino, Black, and Asian immigrants and US-born White adults. The analysis included 145 149 adults (83.60% US-born White adults, 9.55% Latino immigrants, 1.89% Black immigrants, and 4.96% Asian immigrants), with a mean age of 50 years and 53.62% women. Latino (adjusted odds ratio [aOR], 0.92 [95% CI, 0.91-0.93]) and Asian (aOR, 0.93 [95% CI, 0.92-0.94]) immigrants were less likely to have blood pressure screening than US-born White adults. Latino (aOR, 1.22 [95% CI, 1.19-1.25]), Black (aOR, 1.15 [95% CI, 1.09-1.21]), and Asian (aOR, 1.12 [95% CI, 1.08-1.15]) immigrants were more likely to have fasting blood glucose screening, and Latino (aOR, 1.11 [95% CI, 1.09-1.13]), Black or (aOR, 1.12 [95% CI, 1.09-1.16]), and Asian (aOR, 1.05 [95% CI, 1.04-1.07]) immigrants were more likely to have blood cholesterol screening than US-born White adults.

Conclusions: Latino and Asian immigrants have lower odds of annual blood pressure screenings than US-born White adults. More studies exploring facilitators and barriers to the accessibility and use of heart health screenings are needed.

Background: Multicenter electronic health records can support quality improvement and comparative effectiveness research in stroke. However, limitations of electronic health record-based research include challenges in abstracting key clinical variables, including stroke severity, along with missing data. We developed a natural language processing model that reads electronic health record notes to directly extract the National Institutes of Health Stroke Scale score when documented and predict the score from clinical documentation when missing.

Methods and results: The study included notes from patients with acute stroke (aged ≥18 years) admitted to Massachusetts General Hospital (2015-2022). The Massachusetts General Hospital data were divided into training/holdout test (70%/30%) sets. We developed a 2-stage model to predict the admission National Institutes of Health Stroke Scale, obtained from the GWTG (Get With The Guidelines) stroke registry. We trained a model with the least absolute shrinkage and selection operator. For test notes with documented National Institutes of Health Stroke Scale, scores were extracted using regular expressions (stage 1); when not documented, least absolute shrinkage and selection operator was used for prediction (stage 2). The 2-stage model was tested on the holdout test set and validated in the Medical Information Mart for Intensive Care (2001-2012) version 1.4, using root mean squared error and Spearman correlation. We included 4163 patients (Massachusetts General Hospital, 3876; Medical Information Mart for Intensive Care, 287); average age, 69 (SD, 15) years; 53% men, and 72% White individuals. The model achieved a root mean squared error of 2.89 (95% CI, 2.62-3.19) and Spearman correlation of 0.92 (95% CI, 0.91-0.93) in the Massachusetts General Hospital test set, and 2.20 (95% CI, 1.69-2.66) and 0.96 (95% CI, 0.94-0.97) in the MIMIC validation set, respectively.

Conclusions: The automatic natural language processing-based model can enable large-scale stroke severity phenotyping from the electronic health record and support real-world quality improvement and comparative effectiveness studies in stroke.

Background: Unveiling pro-proliferation genes involved in crosstalk between pulmonary artery endothelial cells and pulmonary artery smooth muscle cells (PASMCs) are important to improving the therapeutic outcome of pulmonary hypertension (PH). Although growing studies have shown that super-enhancers (SEs) play a pivotal role in pathological and physiological processes, the SE-associated genes in PH and their impact on PASMC proliferation remain largely unexplored.

Methods and results: We used serotype 5 adenovirus-associated virus to interfere with syndecan-4 and constructed an SU5416 combined with hypoxia-PH model. Chromatin immunoprecipitation sequencing analysis, chromatin immunoprecipitation quantitative polymerase chain reaction, and bioinformatics were used to confirm early growth response 1 was involved in regulating syndecan-4-associated SE in PASMCs. The effects of syndecan-4 and its underlying mechanisms were subsequently elucidated using Western blot, coimmunoprecipitation, and cell coculture assays. Herein, we identified a novel SE-associated gene, syndecan-4, in hypoxia-exposed PASMCs. Syndecan-4 was transcriptionally driven by early growth response 1 via an SE and was significantly overexpressed in hypoxic PASMCs and plasma from patients with PH. Mechanism studies revealed that syndecan-4 induces PASMC proliferation by interacting and regulating protein kinase C α ubiquitination. In addition, syndecan-4 was enriched in exosomes secreted from hypoxic PASMCs, which subsequently transported and led to pulmonary artery endothelial cell dysfunction. Syndecan-4 inhibition in hypoxia by serotype 5 adenovirus-associated virus treatment attenuated the pulmonary artery remodeling and development of PH in vivo.

Conclusions: Taken together, our results demonstrate that an SE-driven syndecan-4 modulates crosstalk of PASMCs and pulmonary artery endothelial cells and promotes vascular remodeling via the protein kinase C α and exosome pathway, thus providing potential targets for the early diagnosis and treatment of hypoxic PH.

Background: Short sleep duration has been associated with an increased risk of cognitive impairment and dementia. Short sleep is associated with elevated blood pressure, yet the combined insult of short sleep and hypertension on brain health remains unclear. We assessed whether the association of sleep duration with cognition and vascular brain injury was moderated by hypertensive status.

Methods and results: A total of 682 dementia-free participants (mean age, 62±9 years; 53% women) from the Framingham Heart Study completed assessments of cognition, office blood pressure, and self-reported habitual and polysomnography-derived sleep duration; 637 underwent brain magnetic resonance imaging. Linear regressions were performed to assess effect modification by hypertensive status on total sleep time (coded in hours) and cognitive and magnetic resonance imaging outcomes. There was a significant interaction between sleep duration and hypertensive status when predicting executive function/processing speed (Trail Making B-A) and white matter hyperintensities. When results were stratified by hypertensive status, longer sleep duration was associated with better executive functioning/processing speed scores in the hypertensive group (meaning that shorter sleep duration was associated with poorer executive function/processing speed scores) (self-report sleep: β=0.041 [95% CI, 0.012-0.069], P=0.005; polysomnography sleep: β=0.045 [95% CI, 0.002-0.087], P=0.038), but no association was observed for the normotensive group. Similarly, shorter subjective sleep duration was associated with higher white matter hyperintensity burden in the hypertensive group (β=-0.115 [95% CI, -0.227 to -0.004], P=0.042), but not in the normotensive group.

Conclusions: In individuals with hypertension, shorter sleep duration was associated with worse cognitive performance and greater brain injury.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease that causes lower extremity arterial stenosis or occlusion. Patients with PAD are at increased risk of myocardial infarction, stroke, limitations in ambulation, and amputation. Despite the advances in medicine and technology, the outcomes from PAD, including critical limb-threatening ischemia, acute limb ischemia amputation, and mortality, remain increased among specific racial and ethnic groups that have been historically marginalized in America, including Black, Hispanic, and American Indian individuals in the United States when compared with White persons. The purpose of this review is to summarize PAD literature that incorporates racial and ethnic disparities in PAD. There are a rising number of studies focused on the interface of racial and ethnic disparities and PAD. The majority of these studies are specifically focused on Black race, whereas there are limited studies focused on other minoritized racial and ethnic groups in the United States. The application of race and ethnicity has also been shown to play a synergistic role with socioeconomic status on PAD outcomes. Effective strategies focused on implementing policies that support quality measures and focus on social determinants of health have been shown to promote health equity and reduce disparities. Current evidence suggests that biological differences are less likely to be the leading cause of disparities in PAD between racial and ethnic groups compared with White Americans and supports a renewed focus on social determinants of health to achieve health equity.

Background: A subset of individuals with major depressive disorder (MDD) have a high burden of cardiovascular risk factors and cerebral small-vessel disease, implicating vascular disease in the development of depression. Cross-sectional studies demonstrate a link between endothelial dysfunction and MDD, but the prospective association between peripheral endothelial dysfunction (PED) and an incident diagnosis of MDD is unknown.

Methods and results: Patients undergoing a baseline assessment of cardiovascular risk were evaluated for PED using reactive hyperemia-peripheral arterial tonometry (≤1.8 consistent with PED). Patient medical records were reviewed to identify those who underwent a formal clinical evaluation of MDD after the index PED evaluation. The frequency of PED was compared in those with and without MDD. Logistic regression analyses were performed to assess the association between baseline PED and incident MDD. Between January 2006 and December 2020, 1614 patients underwent testing for PED. Four hundred eighty-four (30.1%) patients underwent a formal evaluation for MDD after (0-15 years) the index procedure (mean±SD age, 52.8±13.8 years; 65.2% women). Of these, 157 (32.4%) had PED and 108 (31.0%) were diagnosed with MDD. Individuals with MDD had a higher frequency of PED (40.2% versus 30.2%; P=0.034) compared with those without MDD. In multivariable analyses, PED was significantly associated with MDD (odds ratio, 2.3 [95% CI, 1.4-3.8]; P<0.001).

Conclusions: PED is significantly associated with incident MDD. Thus, PED may be a useful marker to identify individuals at increased risk of depression who may benefit from more frequent and earlier management strategies.

Background: The lifetime morbidity burden of patients with Ebstein anomaly (EA) has not been well described.

Methods and results: Through an extensive 2-country register-based collaboration, patients diagnosed with EA who were born between 1930 and 2017 were identified in Danish and Swedish nationwide medical registries. Each patient was matched by age and sex with 10 control subjects from the general population. Cox proportional-hazards regression, Fine-Gray competing risk regression, and Kaplan-Meier failure function were used to estimate the morbidity burden. The study included 794 patients diagnosed with EA and 7940 controls, with a median follow-up period of 33 years. Among patients with EA, approximately half (n=442) had isolated EA, and 28% (n=218) had concomitant atrial septal defect. Patients with complex anatomy demonstrated the highest cardiovascular morbidity burden, followed by those with concomitant atrial septal defect and isolated EA. The lifetime cumulative incidence of supraventricular arrhythmia and ventricular preexcitation in patients with EA, with or without atrial septal defect, was approximately 70% and 19%, respectively. Supraventricular arrhythmia substantially increased the risk of ischemic stroke (hazard ratio [HR] 22.6 [95% CI, 11.1-45.9]). Presence of atrial septal defect significantly affected arrhythmia and heart failure burden compared with isolated EA. In the total cohort of patients with EA, supraventricular arrhythmia onset led to an immediate high incidence of heart failure, with a 10-year cumulative incidence of 18%.

Conclusions: The natural history of EA, whether isolated or not, involves a substantial burden of cardiovascular morbidity and thus a highly vulnerable long-term prognosis.

Background: Sesn2 (Sestrin2) is a stress-induced protein that provides protective effects during myocardial ischemia and reperfusion (I/R) injury, while endoplasmic reticulum (ER) stress may be a pivotal mediator of I/R injury. The goal of this study was to determine whether Sesn2-mTOR (mammalian target of rapamycin) signaling regulates ER stress during myocardial I/R.

Methods and results: In vivo cardiac I/R was induced by ligation and subsequent release of the left anterior descending coronary artery in wild-type (WT) and cardiac-specific Sesn2 knockout (Sesn2^cKO) mice. At 6 hours and 24 hours after reperfusion, cardiac function was evaluated, and heart samples were collected for analysis. I/R induced cardiac ER stress and upregulated Sesn2 mRNA and protein levels. Inhibiting ER stress with 4-phenylbutyric acid reduced infarct size by 37.5%, improved cardiac systolic function, and mitigated myocardial cell apoptosis post-I/R. Hearts from Sesn2^cKO mice displayed increased susceptibility to ER stress during I/R compared with WT. Notably, cardiac mTOR signaling was further increased in Sesn2^cKO hearts compared with WT hearts during I/R. In mice with cardiac Sesn2 deficiency, compared with WT, ER lumen was significantly expanded after tunicamycin-induced ER stress, as assessed by transmission electron microscopy. Additionally, pharmacological inhibition of mTOR signaling with rapamycin improved cardiac function after tunicamycin treatment and significantly attenuated the unfolded protein response and apoptosis in WT and Sesn2^cKO mice.

Conclusions: Sesn2 attenuates cardiac ER stress post-I/R injury via regulation of mTOR signaling. Thus, modulation of the mTOR pathway by Sesn2 could be a critical factor for maintaining cardiac ER homeostasis control during myocardial I/R injury.