Circulation最新文献

Groundbreaking achievements in science and medicine have contributed to reductions in cardiovascular disease and stroke mortality over the past 7 decades. Many of these advances were supported through investments by the National Institutes of Health, the global leader in funding biomedical research. This public investment has produced important economic returns, including supporting >400 000 jobs and roughly $93 billion in economic activity in the United States. Unfortunately, public funding has not kept pace with the burden of disease or rates of inflation. As the nation's oldest and largest volunteer organization dedicated to fighting heart disease and stroke, research is critical to the American Heart Association's mission. Given the American Heart Association's unique position in representation of patients, clinicians, and scientists and as a research funder, we offer the following principles to optimize the future of the US biomedical research enterprise in general and the National Institutes of Health in particular. Specifically, the United States should continue to prioritize innovative and impactful research; to improve efficiency and transparency in its peer review process; to lead in translating evidence into practice; to support the current and future biomedical workforce; and to ensure robust and reliable public investment for the future. The American Heart Association reiterates our strong support for the National Institutes of Health and federal agencies that fund and implement biomedical and population-based research initiatives, which yield important economic returns. These agencies are vital to support today's current and future health challenges, to drive foundational science, to improve patient health, to reduce the global disease burden, to address upstream and preventive strategies, and to improve the value of our public health and health care investments.

Background: Periprocedural myocardial injury (PMI) with or without type 4a myocardial infarction (MI) might occur in patients with non-ST-segment-elevation MI (NSTEMI) after percutaneous coronary intervention (PCI). This study investigated the incidence and prognostic relevance of these events, according to current definitions, in patients with NSTEMI undergoing PCI. The best cardiac troponin I (cTnI) threshold of PMI for prognostic stratification is also suggested.

Methods: Consecutive patients with NSTEMI from January 2017 to April 2022 undergoing PCI with stable or falling pre-PCI cTnI levels were enrolled. According to the Fourth Universal Definition of Myocardial Infarction, the study population was stratified into those experiencing (1) PMI with type 4a MI, (2) PMI without type 4a MI, or (3) no PMI. Post-PCI cTnI increase >20% with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit within 48 hours after PCI was used to define PMI. The primary end point was 1-year all-cause mortality, and the secondary end point consisted of major adverse cardiovascular events at 1 year, including all-cause mortality, nonfatal reinfarction, urgent revascularization, nonfatal ischemic stroke, and hospitalization for heart failure. Internal validation was performed in patients enrolled between May 2022 and April 2023.

Results: Among 1412 patients with NSTEMI undergoing PCI with stable or falling cTnI levels at baseline, 240 (17%) experienced PMI with type 4a MI, 288 (20.4%) experienced PMI without type 4a MI, and 884 (62.6%) experienced no PMI. PMI was associated with an increased risk of adverse clinical outcomes, with patients with type 4a MI demonstrating the highest rates of 1-year all-cause mortality and major adverse cardiovascular events. A post-PCI ΔcTnI >20% but ≤40% showed similar outcomes to patients without PMI, whereas >40% was identified as the optimal threshold for prognostically relevant PMI, confirmed in an internal validation cohort of 305 patients.

Conclusions: Periprocedural ischemic events were frequent in patients with NSTEMI undergoing PCI with prognostic implications. A post-PCI ΔcTnI >40%, combined with an absolute postprocedural value of ≥5 times the 99th percentile upper reference limit, was identified as the optimal threshold for diagnosing prognostically relevant PMI. Recognizing these events may improve risk stratification and management of patients with NSTEMI.

Hypertension in pregnancy contributes substantially to maternal morbidity and mortality, persistent hypertension, and rehospitalization. Hypertensive disorders of pregnancy are also associated with a heightened risk of cardiovascular disease, and timely recognition and modification of associated risk factors is crucial in optimizing long-term maternal health. During pregnancy, there are expected physiologic alterations in blood pressure (BP); however, pathophysiologic alterations may also occur, leading to preeclampsia and gestational hypertension. The diagnosis and effective management of hypertension during pregnancy is essential to mitigate maternal risks, such as acute kidney injury, stroke, and heart failure, while balancing potential fetal risks, such as growth restriction and preterm birth due to altered uteroplacental perfusion. In the postpartum period, innovative and multidisciplinary care solutions that include postpartum maternal health clinics can help optimize short- and long-term care through enhanced BP management, screening of cardiovascular risk factors, and discussion of lifestyle modifications for cardiovascular disease prevention. As an adjunct to or distinct from postpartum clinics, home BP monitoring programs have been shown to improve BP ascertainment across diverse populations and to lower BP in the months after delivery. Because of concerns about pregnant patients being a vulnerable population for research, there is little evidence from trials examining the diagnosis and treatment of hypertension in pregnant and postpartum individuals. As a result, national and international guidelines differ in their recommendations, and more studies are needed to bolster future guidelines and establish best practices to achieve optimal cardiovascular health during and after pregnancy. Future research should focus on refining treatment thresholds and optimal BP range peripartum and postpartum and evaluating interventions to improve postpartum and long-term maternal cardiovascular outcomes that would advance evidence-based care and improve outcomes worldwide for people with hypertensive disorders of pregnancy.

The heart is a highly sex-biased organ, as sex shapes innumerable aspects of heart health and disease. Sex chromosomes and sex hormones -testosterone, progesterone, and estrogen- establish and perpetuate the division between male and female myocardium. Of these differentiating factors, the insulating effects of estrogen have been rigorously interrogated and reviewed, whereas the influence of sex chromosomes, testosterone, and progesterone remains in dispute or ill-defined. Here, we synthesize growing evidence that sex chromosomes and sex hormones substantially bias heart form, function, and dysfunction in a context-dependent fashion. The discrete protective functions ascribed to each of the 3 estrogen receptors are also enumerated. Subsequently, we overview obstacles that have historically discouraged the inclusion of female subjects in basic science such as the impact of the female estrus cycle and reproductive senescence on data reliability and reproducibility. Furthermore, we weigh the utility of several common strategies to intercept and rescue sex-specific protection. Last, we warn of common compounds in animal chow and cell culture that interfere with estrogen signaling. In sum, we survey the controversies and challenges that stem from sex-inclusive cardiovascular research, comparing the possible causes of cardiac sex bias, elucidating sex chromosome or hormone-dependent processes in the heart, describing common lapses that imperil female and male cell and animal work, and illuminating facets of the female heart yet unexplored or still uncertain.

Background: Dilated cardiomyopathy (DCM) appears to be diagnosed twice as often in male than in female patients. This could be attributed to underdiagnosis in female patients or sex differences in susceptibility. Up to 30% of cases have an autosomal dominant monogenic cause, where equal sex prevalence would be expected. The aim of this systematic review, meta-analysis, and population study was to assess the sex ratio in patients with DCM, stratified by genetic status, and evaluate whether this is influenced by diagnostic bias.

Methods: A literature search identified DCM patient cohorts with discernible sex ratios. Exclusion criteria were studies with a small (n<100), pediatric, or peripartum population. Meta-analysis and metaregression compared the proportion of female participants for an overall DCM cohort and the following subtypes: all genetic DCM, individual selected DCM genes (TTN and LMNA), and gene-elusive DCM. Population DCM sex ratios generated from diagnostic codes were also compared with those from sex-specific means using the UK Biobank imaging cohort; this established ICD coded, novel imaging-first, and genotype first determined sex ratios.

Results: A total of 99 studies, with 37 525 participants, were included. The overall DCM cohort had a 0.30 female proportion (95% CI, 0.28-0.32), corresponding to a male:female ratio (M:F) of 2.38:1. This was similar to patients with an identified DCM variant (0.31 [95% CI, 0.26-0.36]; M:F 2.22:1; P=0.56). There was also no significant difference when compared with patients with gene-elusive DCM (0.30 [95% CI, 0.24-0.37]; M:F 2.29:1; P=0.81). Furthermore, the ratio within autosomal dominant gene variants was not significantly different for TTN (0.28 [95% CI, 0.22-0.36]; M:F 2.51:1; P=0.82) or LMNA (0.35 [95% CI, 0.27-0.44]; M:F 1.84:1; P=0.41). Overall, the sex ratio for DCM in people with disease attributed to autosomal dominant gene variants was similar to the all-cause group (0.34 [95% CI, 0.28-0.40]; M:F 1.98:1; P=0.19). In the UK Biobank (n=47 549), DCM defined by International Classification of Diseases, 10th revision, coding had 4.5:1 M:F. However, implementing sex-specific imaging-first and genotype-first diagnostic approaches changed this to 1.7:1 and 2.3:1, respectively.

Conclusions: This study demonstrates that DCM is twice as prevalent in male patients. This was partially mitigated by implementing sex-specific DCM diagnostic criteria. The persistent male excess in genotype-positive patients with an equally prevalent genetic risk suggests additional genetic or environmental drivers for sex-biased penetrance.

Registration: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023451944.

Background: Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality and are associated with acute cardiac events in the peripartum period, as well as cardiovascular disease later in life. Despite the robust association between hypertension and atrial fibrillation (AFib), comparatively little is known about HDP and its subtypes as sex-specific risk factors for AFib.

Methods: A population-based retrospective cohort study was conducted, including 771 521 nulliparous women discharged for obstetrical delivery of their first live or stillborn singleton infant between 2002 and 2017 in Ontario, Canada. Data were obtained from record-level, coded, and linked population-based administrative databases housed at ICES. Using competing risks Cox proportional hazards regression, we estimated crude and multivariable-adjusted cause-specific hazard ratios and 95% CIs for associations between history of any HDP (and its 6 subtypes), and AFib before death, as well as all-cause mortality without a previous AFib diagnosis.

Results: Approximately 8% of women were diagnosed with HDP during the 16-year exposure accrual period. The total person-time of follow-up was 7 380 304 person-years, during which there were 2483 (0.3%) incident AFib diagnoses and 2951 (0.4%) deaths. History of any HDP was associated with an increased cause-specific hazard ratios of incident AFib and death without a previous AFib diagnosis (adjusted cause-specific hazard ratios, 1.45 [95% CI, 1.28-1.64] and 1.31 [95% CI, 1.16-1.47], respectively). These associations were observed in relatively young women (median time to event, 7 years postpartum). Associations suggestive of a dose-response relationship were observed, with more severe HDP subtypes and prepregnancy chronic hypertension associated with a 1.5 to 2.2 times higher cause-specific rate of AFib, and a 1.4 to 2.1 times higher cause-specific rate of death compared with no hypertension in pregnancy.

Conclusions: Women exposed to HDP in their first delivery have a significantly increased cause-specific hazard ratios of incident AFib compared to their unexposed counterparts, with higher rates observed in subjects exposed to more severe de novo HDP diagnoses as well as chronic hypertension in pregnancy. These findings underscore the need to consider HDP history in risk calculation/stratification for arrhythmic and nonarrhythmic cardiovascular diseases, improve surveillance of traditional and female-specific cardiovascular disease risk factors, and develop targeted prevention strategies to reduce the occurrence and burden of HDP.