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Purpose of Review: The role of neuroimmune modulation and inflammation in cardiovascular disease has been historically underappreciated. Physiological connections between the heart and brain, termed the heart-brain axis (HBA), are bidirectional, occur through a complex network of autonomic nerves/hormones and cytokines, and play important roles in common disorders., Recent Findings: At the molecular level, advances in the past two decades reveal complex crosstalk mediated by the sympathetic and parasympathetic nervous systems, the renin-angiotensin aldosterone and hypothalamus-pituitary axes, microRNA, and cytokines. Afferent pathways amplify proinflammatory signals via the hypothalamus and brainstem to the periphery, promoting neurogenic inflammation. At the organ level, while stress-mediated cardiomyopathy is the prototypical disorder of the HBA, cardiac dysfunction can result from a myriad of neurologic insults including stroke and spinal injury. Atrial fibrillation is not necessarily a causative factor for cardioembolic stroke, but a manifestation of an abnormal atrial substrate, which can lead to the development of stroke independent of AF. Central and peripheral neurogenic proinflammatory factors have major roles in the HBA, manifesting as complex bi-directional relationships in common conditions such as stroke, arrhythmia, and cardiomyopathy., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.

Background: It remains unclear whether sepsis-related cardiovascular complications have an adverse impact on survival independent of pre-existing comorbidities. To investigate the survival impact of post-sepsis cardiovascular complications among sepsis survivors, we conducted a population-based study using the National Health Insurance Database of Taiwan., Methods: We identified sepsis patients from the National Health Insurance Research Database of Taiwan using ICD-9-CM codes involving infection and organ dysfunction between 2000 and 2011. Post-sepsis incident myocardial infarction (MI) and stroke were ascertained by ICD-9-CM codes and antiplatelet treatment. We constructed a non-sepsis comparison cohort using propensity score matching to ascertain the association between sepsis and cardiovascular complications. Furthermore, we compared the 180-day mortality and 365-day mortality between patients surviving sepsis with or without post-sepsis MI or stroke within 70 days of hospital discharge. We constructed Cox regression models adjusting for pre-existing comorbidities to evaluate the independent survival impact of post-sepsis MI or stroke among sepsis survivors., Results: We identified 42,316 patients hospitalized for sepsis, from which we matched 42,151 patients 1:1 with 42,151 patients hospitalized without sepsis. Compared to patients hospitalized without sepsis, patients hospitalized with sepsis had an increased risk of MI or stroke (adjusted odds ratio 1.72, 95% CI 1.60-1.85). Among 42,316 patients hospitalized for sepsis, 486 (1.15%) patients developed incident stroke and 108 (0.26%) developed incident MI within 70 days of hospital discharge. Compared to sepsis survivors without cardiovascular complications, sepsis survivors with incident MI or stroke had a higher mortality rate at 180 days (11.68% vs. 4.44%, P = 0.003) and at 365 days (16.75% vs. 7.11%, P = 0.005). Adjusting for age, sex, and comorbidities, post-sepsis MI or stroke was independently associated with increased 180-day (adjusted hazard ratio [HR] 2.16, 95% CI 1.69-2.76) and 365-day (adjusted HR 1.90, 95% CI 1.54-2.32) mortality., Conclusions: Compared to sepsis patients without incident MI or stroke, sepsis patients with incident MI or stroke following hospital discharge had an increased risk of mortality for up to 365 days of follow-up. This increased risk cannot be explained by pre-sepsis comorbidities.

Cardiovascular toxicities associated with immune checkpoint inhibitors (ICIs) have been reported in case series but have been underappreciated due to their recent emergence, difficulties in diagnosis and non-specific clinical manifestations. ICIs are antibodies that block negative regulators of the T cell immune response, including cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and PD-1 ligand (PD-L1). While ICIs have introduced a significant mortality benefit in several cancer types, the augmented immune response has led to a range of immune-related toxicities, including cardiovascular toxicity. ICI-associated myocarditis often presents with arrhythmias, may co-exist with myositis and myasthenia gravis, can be severe, and portends a poor prognosis. In addition, pericardial disease, vasculitis, including temporal arteritis, and non-inflammatory heart failure, have been recently described as immune-related toxicities from ICI. This narrative review describes the epidemiology, diagnosis, pathophysiology, and treatment of cardiovascular toxicities of ICI therapy, highlighting recent developments in the field in the past year., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the effect of intensive blood pressure treatment on cardiovascular disease or all-cause mortality differ based on the presence or absence of orthostatic or standing hypotension? Findings: In this individual data meta-analysis of more than 29 000 participants in 9 hypertension trials, more intensive blood pressure treatment lowered risk of cardiovascular disease or all-cause mortality regardless of whether participants had orthostatic hypotension. Moreover, effects did not differ by the presence or absence of standing hypotension. Meaning: Asymptomatic orthostatic hypotension or standing hypotension among adults with hypertension should not be a deterrent to more intensive hypertension treatment. Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension. Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments. Data Extraction and Synthesis: Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach. Main Outcomes and Measures: Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less. Results: The 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P =.68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P =.16 for interaction of treatment with baseline standing hypotension). Conclusions and Relevance: In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension. This individual participant data meta-analysis assesses the effect of a lower blood pressure (BP) treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease or all-cause mortality among adults with orthostatic hypotension or standing hypotension. [ABSTRACT FROM AUTHOR]