Relation between markers of systemic vascular inflammation and smoking in women☆

Smoking is known to be associated with an increased risk of intracranial aneurysm rupture; however, the risk in smokers stratified by age, sex, and aneurysm location is not clear.

A retrospective study of all aneurysmal subarachnoid hemorrhage (aSAH) cases in Australia between 2008 and 2018 was conducted. The relative risk of aSAH in smokers compared with nonsmokers was calculated on the basis of nationwide smoking statistics and was stratified according to sex, age group, and aneurysm location.

Out of 12,915 aSAH patients, 3249 (25.2%) were active smokers. Across both men and women, smoking increased the risk of aSAH by 2.4× in 30- to 39-year-olds (95% CI 2.1–2.7), 2.4× in 40- to 49-year-olds (95% CI 2.2–2.7), 2.3× in 50- to 59-year-olds (95% CI 2.1–2.4), and 1.8× in 60- to 69-year-olds (95% CI 1.7–2.0) with less of an effect in smokers younger than 30 years (RR: 1.2, 95% CI 1.0–1.5) and older than 70 years (RR: 1.0, 95% CI 0.9–1.2). Compared with a nonsmoker younger than 30 years old, the relative risk of aSAH increased by an average of 7.2 for every decade spent smoking in women and an average of 4.0 for every decade spent smoking in men. Additionally, smokers were 5.2× more likely to present before 50 years of age.

Smoking increased the risk of aSAH by 2-fold between the ages of 30 and 60. Smokers experienced aSAH at younger ages.

Worldwide, the two leading causes of death are cardiovascular disease (CVD) and cancer. Although considered as two separate disease entities, CVD and cancer possess several similarities and interactions, including a number of common risk factors (genetic and environmental) which are suggestive of a shared biology among the diseases. Trails of documented evidence from the literature have supported the statement that after secondary malignancies, cardiovascular disease is the leading cause of late morbidity and death among cancer survivors. This increased burden of cardiovascular disease results from the interplay of various factors. Adequate cardiovascular risk assessment and timely intervention through a multidisciplinary approach in cancer survivors plays a pivotal role in the prevention of cardiovascular morbidity and mortality.

Cardiovascular risk factors have a major impact on subsequent treatment-related cardiotoxicity and are prevalent in cancer survivors. There is an immediate need for the widespread availability of cardiovascular preventive services to reduce the late adverse effects of chemotherapy and radiation. In this chapter, we explore the risk factors and management of CVD in cancer survivors.

Tobacco smoking and hemodynamic forces are key stimuli for the development of endothelial dysfunction. As an alternative to smoking, next generation tobacco and nicotine products (NGP) are now widely used. However, little is known about their potential pro-inflammatory and atherogenic effects on the endothelium. In this study, we analyzed key parameters of endothelial function after exposure to aqueous smoke extracts (AqE) of a heated tobacco product (HTP), an electronic cigarette (e-cig), a conventional cigarette (3R4F) and pure nicotine. All experiments were performed under atheroprotective high laminar or atherogenic low flow with primary human endothelial cells.

Treatment with 3R4F, but not alternative smoking products, reduced endothelial cell viability and wound healing capability via the PI3K/AKT/eNOS(NOS3) pathway. Laminar flow delayed detrimental effects on cell viability by 3R4F treatment. 3R4F stimulation led to activation of NRF2 antioxidant defense system at nicotine concentrations ≥0.56 μg/ml and increased expression of its target genes HMOX1 and NQO1. Treatment with HTP revealed an induction of HMOX1 and NQO1 at dosages with ≥1.68 μg/ml nicotine, whereas e-cig and nicotine exposure had no impact. Analyses of pro-inflammatory genes revealed an increased ICAM1 expression under 3R4F treatment. 3R4F reduced VCAM1 expression in a dose-dependent manner; HTP treatment had similar but milder effects; e-cig and nicotine treatment had no impact. SELE expression was induced by 3R4F under static conditions. High laminar flow prevented this upregulation. Stimulation with laminar flow led to downregulation of CCL2 (MCP-1). From this downregulated level, only 3R4F increased CCL2 expression at higher concentrations. Finally, under static conditions, all components increased adhesion of monocytes to endothelial cells. Interestingly, only stimulation with 3R4F revealed increased monocyte adhesion under atherosclerosis-prone low flow.

In conclusion, all product categories activated anti-oxidative or pro-inflammatory patterns. NGP responses were typically lower than in 3R4F exposed cells. Also, 3R4F stimulation led to an impaired endothelial wound healing and induced a pro-inflammatory phenotype compared to NGP treatment.

Smoking is the leading cause of morbidity and mortality worldwide and is clearly involved as a cardiovascular risk factor. Smoking has different effects on the cardiovascular system, such as a decrease in nitric oxide, increased inflammatory response, increased adhesion of pro-atherogenic molecules, lipid disturbances, generation of oxidative stress and endothelial dysfunction as can be shown in different biomarkers modifications. Despite the aids currently available for smoking cessation, many smokers are unwilling or unable to achieve this. So alternative tools with potential harm reduction, such as non-combustion tobacco products, could be an option due to the better results they had shown on cardiovascular risk factors. This has led these devices to be taken into account as a risk-modifying tobacco product according to the FDA.

El tabaquismo es la principal causa de morbimortalidad a nivel mundial y tiene una implicación clara como factor de riesgo cardiovascular. El tabaco posee distintos efectos a nivel cardiovascular, como son una disminución del óxido nítrico, aumento de la respuesta inflamatoria, aumento de la adhesión de moléculas proaterogénicas, modificaciones lipídicas, generación de estrés oxidativo y disfunción endotelial que puede verse reflejada en distintos biomarcadores. A pesar de las ayudas que se poseen actualmente para la cesación tabáquica, parte de la población consumidora no quiere o no lo puede conseguir y es por ello que herramientas alternativas como los productos de reducción del daño y el tabaco por calentamiento podrían ser una opción gracias a los mejores resultados que muestran sobre los factores de riesgo cardiovascular comparado con el cigarrillo convencional. Algo que ha llevado a estos dispositivos para ser considerados como producto de tabaco modificador del riesgo, según la FDA.

Sexually-diverse individuals (those who seek sexual or romantic relationships with the same and/or multiple genders) and gender-diverse individuals (those whose gender identity and/or expression differs from their birth-assigned sex/gender) have disproportionately high physical health problems, but the underlying biological causes for these health disparities remain unclear. Building on the minority stress model linking social stigmatization to health outcomes, we argue that systemic inflammation (the body’s primary response to both physical and psychological threats, indicated by inflammatory markers such as C-reactive protein and proinflammatory cytokines) is a primary biobehavioral pathway linking sexual and gender stigma to physical health outcomes. Expectations and experiences of social threat (i.e., rejection, shame, and isolation) are widespread and chronic among sexually-diverse and gender-diverse individuals, and social threats are particularly potent drivers of inflammation. We review research suggesting that framing “minority stress” in terms of social safety versus threat, and attending specifically to the inflammatory consequences of these experiences, can advance our understanding of the biobehavioral consequences of sexual and gender stigma and can promote the development of health promoting interventions for this population.