Cardiovascular Effects Research Articles

PM2.5 toxicity in blood impairs cardiac redox balance and promotes mitochondrial dysfunction in rat heart that further aggravates ischemia reperfusion injury by modulating PI3K/AKT/mTOR/NF-kB signaling axis.

According to the pathophysiological mechanisms linking particulate matter (PM2.5) exposure and cardiovascular diseases, PM2.5 may directly translocate into the blood stream and remote target organs and thereby induce cardiovascular effects. The toxicity of PM2.5 is known to induce oxidative stress in pulmonary tissue, but its impact on the redox state in heart (distant organ) is unknown and how it modulates the cardiac response to ischemia reperfusion (IR) remains unclear. In the present study, we evaluated the toxic effect of PM2.5 on cardiac physiology in the presence and absence of IR after introducing PM2.5 into the blood. Female Wistar rats were injected with diesel particulate matter (DPM) via i.p & i.v routes at a concentration of 10 µg/ml. The toxic impact of PM2.5 not only adversely affects the cardiac ultra-structure (leading to nuclear infiltration, edema, irregularities in heart muscle and nuclear infiltration), but also altered the cellular redox balance, elevated inflammation and promoted the upregulation of proapoptotic mediator genes at the basal level of myocardium. The results showed alterations in cardiac ultrastructure, elevated oxidative stress and significant redox imbalance, increased inflammation and proapoptotic mediators at the basal level of myocardium. Moreover, the cardioprotective pro survival signaling axis was declined along with an increased NF-kB activation at the basal level. IR inflicted further injury with deterioration of cardiac hemodynamic indices (Heart rate [HR], Left ventricular developed pressure [LVDP], Left ventricular end-diastolic pressure [LVEDP] and rate pressure product [RPP]) along with prominent inactivation of signaling pathways. Furthermore, the levels of GSH/GSSG, NADH/NAD, NADPH/NADP were significantly low along with increased lipid peroxidation in mitochondria of PM2.5 treated IR rat hearts. This observation was supported by downregulation of glutaredoxin and peroxiredoxin genes in the myocardium. Similarly the presence of oxidative stress inducing metals was found at a higher concentration in cardiac mitochondria. Thus, the toxic impact of PM2.5 in heart augment the IR associated pathological changes by altering the physiological response, initiating cellular metabolic alterations in mitochondria and modifying the signaling molecules.

Olanzapine-induced cardiomyopathy: A mimicker of obesity cardiomyopathy?

Olanzapine, an atypical antipsychotic medication, has gained prominence in the treatment of schizophrenia and related psychotic disorders due to its effectiveness and perceived safety profile. However, emerging evidence suggests a potential link between olanzapine use and adverse cardiovascular effects, including cardiomyopathy. This narrative review explores the mechanisms, clinical implications, and management strategies associated with olanzapine-induced cardiomyopathy. A comprehensive review of the literature was conducted to investigate the relationship between olanzapine and cardiomyopathy. The search included epidemiological studies, clinical case reports, and mechanistic research focusing on the pathophysiology of olanzapine-induced cardiomyopathy. The review also examined treatment strategies for managing this potential complication. Olanzapine-induced cardiomyopathy is hypothesized to be associated with metabolic disturbances and receptor antagonism. The metabolic effects of olanzapine, such as weight gain, insulin resistance, and dyslipidemia, share similarities with obesity-related cardiomyopathy. Additionally, olanzapine's antagonism of certain receptors may contribute to cardiovascular stress. The review highlighted that patients with new-onset heart failure and significant weight gain while on olanzapine should be closely monitored for signs of cardiomyopathy. Early detection and prompt withdrawal of olanzapine, along with initiation of goal-directed medical therapy, are crucial for mitigating this potentially life-threatening condition. The relationship between olanzapine and cardiomyopathy is complex and not yet fully understood. However, the potential for significant cardiovascular risk necessitates vigilance among healthcare providers. Early identification and management of olanzapine-induced cardiomyopathy can improve patient outcomes. Further research is needed to elucidate the precise mechanisms behind this adverse effect and to develop optimized treatment strategies for patients requiring antipsychotic therapy.

The Protective Role of Resilience on Cardiovascular Health in Young Adults Exposed to Adverse Childhood Experiences

Background: Adverse childhood experiences (ACEs) are strong emotional or physical stressors that occur during sensitive developmental periods and are associated with reduced cardiovascular health (CVH). Resilience, or the psychological capacity of individuals to cope with adversity, has been recently shown to have a positive influence on CVH. Despite the dose-dependent detrimental impact of ACEs on CVH, it is unknown whether resilience exerts a protective cardiovascular effect against early stress. Thus, the purpose of this study was to investigate the impact that resilience may have on CVH in young adults who experienced ACEs. Methods: Eighteen young and apparently healthy adults (22±3 yo) with a history of severe ACE exposure (≥4) participated in this study and provided self-reported data about resilience. CVH was assessed non-invasively through transcutaneous arterial tonometry to evaluate arterial stiffness (pulse-wave velocity, PWV), myocardial oxygen demand (Systolic Pressure Time Index, SPTI), myocardial oxygen supply (Diastolic Pressure Time Index, DPTI) and myocardial perfusion (Subendocardial Viability Ratio, SEVR). Circulating biomarkers related to CVH were also evaluated (high-sensitive C-reactive protein, hsCRP). Results: Eleven participants reported high resilience (HR: resilience score≥95), while seven reported low resilience (LR: resilience score<95). Young adults with high resilience presented with a significantly lower myocardial oxygen demand (SPTI; HR: 1866±111 vs. LR: 2227±117mmHg·s/min, p=0.047) and higher myocardial perfusion (SEVR; HR: 168±13 vs.LR: 127 ±9% , p=0.034) than those with low resilience and a positive association between SEVR and resilience was identified ( r=0.492; p=0.045). No differences in myocardial oxygen supply ( p=0.225) or arterial stiffness ( p=0.614) were observed between groups. However, circulating hsCRP was also significantly lower in the HR group than the LR (0.89±0.3 vs. 2.96±1 mg/dL, p=0.041) and negatively associated with resilience ( r=-0.511; p=0.051). Conclusions: Our data suggests that, among young and apparently healthy adults exposed to childhood adversity, those who are psychologically more resilient exhibit higher myocardial perfusion and overall better CVH than those less resilient despite a history of severe ACEs. These findings suggest that resilience may protect, at least partially, against the early impact of ACEs on CVH. Future studies are thus warranted to further explore the relationship between resilience and CVH. Supported in part by the Child Health Research Institute at VCU. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiorenal Effects of Chronic High Phosphate Diet in Female Rats

Cardiorenal Syndrome Type 4 (CRS4) refers to the development of cardiovascular dysfunction as a result of chronic kidney disease. The accumulation of circulating phosphate in the later stages of chronic kidney disease (CKD) has been positively associated with cardiac hypertrophy and dysfunction. In our previous work, we found that male Sprague Dawley rats that underwent 5/6 nephrectomy (5/6Nx) to induce CKD phenotypes also developed cardiac pathology when serum phosphorus levels became elevated. Small RNA sequencing of left ventricle tissue revealed upregulated microRNA-21-5p and -3p expression in 5/6Nx rats, when compared to sham-operated controls, and suppression of miR-21-5p attenuated left ventricle pathology in male 5/6Nx rats. We hypothesize that hyperphosphatemia, independent of CKD, can impair cardiac function and that miR-21 may mediate these effects. It has been recently reported that females exhibit higher urinary phosphate excretion in response to high dietary phosphate intake than males. In this study, hyperphosphatemia was induced by placing 9-week old female wild-type (WT) Sprague Dawley and global miR-21 knockout (miR-21−/−; lacking both miR-21-5p and -3p rats) (n=4-9/group) on either high phosphate (2% Pi) or control diet (0.6% Pi) for 8 weeks. Echocardiography and renal ultrasound were performed under anesthesia to assess cardiac function and renal cross-sectional area, respectively, prior to tissue collection at endpoint. Rats of either genotype fed 2% Pi diet exhibited increased left kidney weight, left kidney/body weight, and left kidney cross-sectional area (2-way ANOVA, main effect of diet; p<0.05). In animals fed 2% Pi, miR-21−/− rats had significantly higher left ventricle fractional shortening than WT rats (57.06 ± 3.32 vs. 43.96 ± 1.34; 2-way ANOVA with Tukey multiple comparisons; p<0.05). This study allowed the cardiovascular effects of chronically elevated phosphate to be isolated from other uremic toxins elevated in CKD. We find that loss of miR-21 augments cardiac function, supporting a role for miR-21 in mediating phosphate-related pathology. Ongoing studies are focused on identifying specific molecular mechanisms driving these changes. This study was supported by T32HL007852 and R01HL128332. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Aldosterone applied mucosally or serosally is equally effective in stimulating ENaC activity in rat distal colon

Background: Aldosterone (ALDO), a mineralocorticoid hormone, is essential for regulating blood volume and electrolyte homeostasis. ALDO acts via intracellular mineralocorticoid receptors to stimulate epithelial Na+ channel (ENaC)-mediated Na+ absorption and large conductance K+ (BK) channel-mediated K+ secretion in both kidney and distal colon. We recently showed that ALDO stimulates iron absorption in rat distal colon and SK-CO15 cells (human colon cancer cell line), raising the prospect that ALDO might be used as adjuvant therapy in iron-deficient patients refractory to oral iron. Since, parenteral ALDO (or Fludrocortisone, a synthetic mineralocorticoid agonist) would adversely affect cardiovascular function, an alternative route of administration is required. Parenteral ALDO gains access to target epithelial cells via their serosal (basolateral) membranes, and in vitro studies have always employed serosally applied ALDO to determine its effects on colonic ion transport, but it is not known if mucosally (apically) applied ALDO has similar effects. Hypothesis: We hypothesized that like serosal ALDO, mucosal ALDO would diffuse across apical cell membranes and induce ENaC activity in normal rat distal colon. Aim: To determine whether mucosally applied ALDO stimulates amiloride-sensitive electrogenic Na+ transport in rat distal colon. Methods: Muscularis stripped normal rat (Sprague-Dawley; 126 – 150 g) distal colon was mounted under voltage clamp condition in Ussing chambers. ALDO (10 mM) was added to either the mucosal or serosal bath. ENaC activity was measured as the change in short-circuit current (Isc) following the mucosal addition of amiloride (10 mM). ALDO in mucosal and serosal bath solutions was measured using mass-spectroscopy. Results: With serosal addition of ALDO, transcriptionally induced ENaC activity began to increase after 4 hr and reached maximum/plateau by 5 hr. By contrast, with mucosal addition of ALDO, ENaC activity began to increase after 8 hr and slowly reached maximum/plateau by 9.5 hr. Maximal amiloride-sensitive ENaC activities were similar irrespective of whether ALDO was applied mucosally or serosally. Following addition of ALDO to the mucosal or serosal bath, a similar amount (40%) of ALDO had moved from mucosa to serosa or serosa to mucosa after 24 hr. Conclusions: We conclude that: (1) ALDO induces ENaC activity to the same extent, whether applied mucosally or serosally, and (2) the delayed effect of mucosally applied ALDO may reflect slower diffusion across apical membranes than across basolateral membranes. We speculate that developing a colon-specific delivery system may avoid the adverse cardiovascular effects of oral mineralocorticoid agonists (e.g. Fludrocortisone) if used to enhance colonic iron absorption in iron-deficient patients refractory to oral iron. Transition GrantSupport; Offce of Research and Graduate Education, WVU Health Sciences Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The impact of intravenous medetomidine and vatinoxan on echocardiographic evaluation of dogs with stage B1 mitral valve disease

Introduction / objectiveThe purpose of this study was to investigate the echocardiographic effects of intravenous medetomidine and vatinoxan in dogs with stage B1 mitral valve disease. We hypothesised medetomidine-vatinoxan would reduce the need for manual restraint during echocardiography without producing detrimental cardiovascular effects or echocardiographic changes. AnimalsTwelve client owned dogs with stage B1 mitral valve disease. MethodsA transthoracic echocardiographic examination was performed before and after sedation with intravenous medetomidine (10 μg/kg) and vatinoxan (200 μg/kg). Vital parameters were also recorded, and the level of sedation was assessed subjectively. The data were analysed with Student’s t-tests with an alpha-level of <0.05. ResultsEnd-systolic volume and left ventricular systolic diameter increased (from 0.89 ± 0.19 mL/kg to 1.13 ± 0.29 mL/kg and 0.96 ± 0.12 cm to 1.10 ± 0.10 cm, respectively) and ejection fraction (from 66.33 ± 4.0% to 56.23 ± 9.54%) and fractional shortening (from 36.13 ± 5.42% to 27.24 ± 5.6%) decreased significantly after sedation. End diastolic volume, left ventricular diastolic diameter, and left atrial size remained statistically unchanged, while aortic (from 1.34 ± 0.2 m/s to 0.99 ± 0.14 m/s) and pulmonic (from 0.94 ± 0.16 m/s to 0.66 ± 0.15 m/s) velocities decreased significantly. No dogs had a mean arterial pressure below 65 mmHg. Sedation enabled echocardiographic examination without manual restraint. No adverse effects were observed with the dose studied. ConclusionsEchocardiographic parameters were not completely comparable with the baseline values, which should be taken into consideration when evaluating dogs sedated with intravenous medetomidine-vatinoxan.

EXPLORING THE EFFECTS OF VIGOROUS INTERVAL TRAINING, MODERATE RESISTANCE TRAINING AND PILATES ON ARTERIAL STIFFNESS AND BLOOD PRESSURE DURING PREGNANCY: A RANDOMISED CROSS-OVER TRIAL

INTRODUCTION Regular moderate intensity exercise throughout pregnancy provides significant benefits to both maternal and foetal cardiovascular health outcomes. Current exercise guidelines recommend a combination of moderate intensity aerobic and resistance training (RT). However, there is limited research exploring the cardiovascular effects of higher intensities (vigorous/high) in comparison to common pregnancy exercise modalities such as RT and Pilates (PIL). AIM: To investigate the acute effects of three modes of exercise (resistance, vigorous aerobic intervals and Pilates) during trimester two (T2) and three (T3) of pregnancy on measures of arterial stiffness (pulse wave velocity [PWV]) and blood pressure (BP). METHODS Eleven women with uncomplicated pregnancies (age 32 ± 3 years, pre-pregnancy BMI 23.9 ± 3.5 kg/m2) completed testing in T2 (average 20 ± 1.6 weeks gestation) and T3 (average 29 ± 2.5 weeks gestation). Participants performed one each of vigorous intensity interval training (VIIT) (∼33 min), resistance training (RT) (∼35 min) and Pilates (PIL) (∼35 min) in T2 and T3 in randomised order approximately 1 week apart each trimester. Resting outcome measures of PWV, BP and foetal heart rate (FHR) were obtained following 5 minutes of rest and again immediately and 10 minutes post exercise session. BP, maternal heart rate (MHR), and rating of perceived exertion (RPE) were monitored throughout. RESULTS There was no difference in the acute PWV response to each type of exercise across the trimesters (1 min VIIT: T2 = 5.53 ± 0.85m/s, T3 = 5.26 ± 0.67m/s, 95%CI[-1.36-0.67]; RT: T2 = 5.4 ± 0.80m/s, T3 = 5.48 ± 0.56m/s, 95%CI[-0.88-1.10]; PIL: T2 = 5.44 ± 0.68m/s, T3 = 5.44 ± 0.68m/s, 95%CI[-0.93-1.01]). There was no significant difference in the acute response in SBP to VIIT (T2 = 116 ± 12.1mmHg, T3 = 122 ± 7.2mmHg, 95%CI[-0.42 - 1.65]. SBP was significantly higher in T3 than T2 1 minute following PIL (T2 = 110 ± 5.8mmHg, T3 = 121 ± 11.7mmHg, 95%CI[0.04-2.1]) and 10 minutes following RT (T2 = 105 ± 10.1mmHg, T3 = 116 ± 5.0mmHg, 95%CI[0.27 - 2.46]. CONCLUSION VIIT, RT and PIL appear to elicit similar post-exercise haemodynamic and arterial stiffness responses in both the mother and foetus. As such, VIIT may be a suitable addition to standard moderate intensity and RT prescription during an uncomplicated pregnancy.

Comparative Study of Cardiovascular Effects of Selected Pulmonary Vasodilators in Canine Models of Mitral Valve Disease.

Previous reports have shown that various oral pulmonary vasodilators are effective against canine pulmonary hypertension (PH). However, no studies have compared their hemodynamic effects. We aimed to compare the hemodynamic effects of 15 µg/kg beraprost sodium, 1.0 mg/kg sildenafil, and their combination, in dogs with experimentally induced mitral regurgitation. This experimental crossover study evaluated the hemodynamic and functional effects of oral pulmonary vasodilators by application of right-sided heart catheterization and echocardiography. Beraprost significantly decreased pulmonary and systemic vascular resistance. Additionally, beraprost increased right-ventricular stroke volume and left-ventricular cardiac output without worsening left-heart size and left-atrial pressure. The pulmonary vasodilatory effects of sildenafil were stronger, and its systemic vasodilatory effects were weaker than those of beraprost. However, sildenafil significantly increased the left-ventricular volume, left-atrial pressure indicator, and right-ventricular cardiac output. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart size and left-atrial pressure indicators. Both beraprost and sildenafil were effective against canine PH; however, sildenafil was associated with the risk of worsening left-heart loading. Combination therapy with beraprost and sildenafil synergistically dilated pulmonary and systemic vessels, indicating a more potent treatment option for severe PH cases.

Sleep deprivation reduces the baroreflex sensitivity through elevated angiotensin (Ang) II subtype 1 receptor expression in the nucleus tractus solitarii.

Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation. Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed. Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation. In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation.

Polystyrene microplastics enhance microcystin-LR-induced cardiovascular toxicity and oxidative stress in zebrafish embryos

The health risks associated with combined exposure to microplastics (MPs) and cyanobacteria toxins have gained increasing attention due to the large-scale prevalence of cyanobacterial blooms and accumulation of MPs in aquatic environments. Therefore, we explored the cardiovascular toxic effects of microcystin-LR (MC-LR, 1, 10, 100 μg/L) in the presence of 5 μm polystyrene microplastics (PS-MPs, 100 μg/L) and 80 nm polystyrene nanoplastics (PS-NPs, 100 μg/L) in zebrafish models. Embryos were exposed to certain PS-MPs and PS-NPs conditions in water between 3 h post-fertilization (hpf) and 168 hpf. Compared to MC-LR alone, a significant decrease in heart rate was observed as well as notable pericardial edema in the MC-LR + PS-MPs/NPs groups. At the same time, sinus venosus and bulbus arteriosus (SV-BA) distances were significantly increased. Furthermore, the addition of PS-MPs/NPs caused thrombosis in the caudal vein and more severe vascular damage in zebrafish larvae compared to MC-LR alone. Our findings revealed that combined exposure to PS-NPs and MC-LR could significantly decreased the expression of genes associated with cardiovascular development (myh6, nkx2.5, tnnt2a, and vegfaa), ATPase (atp1a3b, atp1b2b, atp2a1l, atp2b1a, and atp2b4), and the calcium channel (cacna1ab and ryr2a) compared to exposure to MC-LR alone. In addition, co-exposure with PS-MPs/NPs exacerbated the MC-LR-induced reactive oxygen species (ROS) production, as well as the ROS-stimulated apoptosis and heightened inflammation. We also discovered that astaxanthin (ASTA) treatment partially attenuated these cardiovascular toxic effects. Our findings confirm that exposure to MC-LR and PS-MPs/NPs affects cardiovascular development through calcium signaling interference and ROS-induced cardiovascular cell apoptosis. This study highlights the potential environmental risks of the co-existence of MC-LR and PS-MPs/NPs for fetal health, particularly cardiovascular development.

Transportation Noise Pollution and Cardiovascular Health.

Epidemiological studies have found that transportation noise increases the risk for cardiovascular morbidity and mortality, with solid evidence for ischemic heart disease, heart failure, and stroke. According to the World Health Organization, at least 1.6 million healthy life years are lost annually from traffic-related noise in Western Europe. Traffic noise at night causes fragmentation and shortening of sleep, elevation of stress hormone levels, and increased oxidative stress in the vasculature and the brain. These factors can promote vascular (endothelial) dysfunction, inflammation, and arterial hypertension, thus elevating cardiovascular risk. The present review focusses on the indirect, nonauditory cardiovascular health effects of noise. We provide an updated overview of epidemiological research on the effects of transportation noise on cardiovascular risk factors and disease, and mechanistic insights based on the latest clinical and experimental studies and propose new risk markers to address noise-induced cardiovascular effects in the general population. We will discuss the potential effects of noise on vascular dysfunction, oxidative stress, and inflammation in humans and animals. We will elaborately explain the underlying pathomechanisms by alterations of gene networks, epigenetic pathways, circadian rhythm, signal transduction along the neuronal-cardiovascular axis, and metabolism. We will describe current and future noise mitigation strategies. Finally, we will conduct an overall evaluation of the status of the current evidence of noise as a significant cardiovascular risk factor.

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

A panel study of exposure to fine particulate matter and modeled respiratory deposition on biomarkers of inflammation, blood coagulation, and oxidative stress in healthy young adults in Hefei, China

Evidence is scarce on the acute cardiovascular health effects of fine particulate matter (PM2.5) and its respiratory tract depositions. We performed a panel study in Hefei, China to explore the relations of PM2.5 and its depositions in 3 respiratory tract regions over different lag times with a range of cardiovascular biomarkers among 40 college students and the potential mediating effects of inflammation. We found significant effects of PM2.5 exposure on the alterations of biomarkers at specific lag days, in a concentration-response manner, even at PM2.5 level below Chinese Ambient Air Quality Standard (CAAQS) Grade I (35 μg/m3). For example, per 10 μg/m3 increase in PM2.5 concentration was associated with −9.33% increase in ADAMTS13 on lag 0-1d. The corresponding increases in D-Dimer, GM-CSF, and MCP-1 for the same change in PM2.5 concentration on lag 5-6d were 30.51%, 11.43%, and 20.05%. Besides, tracheobronchial region (TB) deposition presented more evident effects on these biomarkers than that in PM2.5. Additionally, we observed greater associations of PM2.5-biomarkers among females, those with abnormal body mass index (BMI), and those with physical activity. The results indicated that short-term PM2.5 exposure and its respiratory tract depositions were concentration-responsive associated with damaged cardiovascular health via inducing blood coagulation, oxidative stress and inflammation among healthy young adults even at concentration below CAAQS Grade I. Elevated serum levels of systemic inflammation may be partly responsible for the effects of PM2.5 and its respiratory tract depositions on coagulation function.

Cardiometabolic impacts of gender-affirming hormone therapy in transgender persons: a systematic review

Introduction: Transgender persons with gender dysphoria can be treated using hormones based on estradiol and testosterone. The long-term cardiovascular effects of these therapies are not fully known. Objective: To verify the impact of gender-affirming hormone therapy on risk factors for cardiovascular events (lipid profile, glucose, and blood pressure) and cardiovascular events (acute myocardial infarction [AMI], stroke, and venous thromboembolism [VTE]) in transgender persons. Methods: A systematic review of scientific articles was performed using the PubMed/MEDLINE, Scopus, Embase, and Web of Science platforms. Results and Discussion: The search resulted in 1040 articles, of which 154 duplicates were discarded. Of the remaining 886, 837 articles were excluded, leaving 49, which were read in full. Among these, after confrontation of two researchers, 14 were selected for interpretation and final data extraction. Regarding the data obtained, 11 articles considered transgender women (TW), resulting in a population of 7154 people, with a mean age of 29 years. When interpreting the results, there was an increase in VTE and stroke events in TW compared to cis men and women. The cardiovascular risk factors did not show significant changes in the evaluated studies. Twelve studies were considered for transgender men (TM), generating a population of 4393 people, with a mean age of 26 years. A worsening of the lipid profile in TM and an increase in AMI were observed in comparison with cis women. Conclusion: Review data showed that transgender persons have a risk of increased cardiovascular outcomes and may require early intervention as a preventive measure.

Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis.

The cardiovascular effects of metformin continue to be a subject of debate within the medical community. The Mendelian randomization (MR) study used data from genome-wide association studies (GWAS) to explore the causal association with six diseases that are associated with bimatoprost treatment and myocardial infarction, chronic heart failure, atrial fibrillation, hypertrophic and dilated cardiomyopathy, and valvular disease. Genome-wide significant single nucleotide polymorphisms (SNPs), that are associated with metformin use were selected as the instrumental variables. To determine the causal relationship between metformin use and various cardiovascular diseases, MR analysis was conducted, employing methods such as Instrumental Variable Weighting (IVW). The IVW analysis demonstrated a positive association between metformin treatment and the risk of myocardial infarction (OR = 22.67, 95% CI 3.22-34.01; P = 0.002). Conversely, metformin treatment exhibited a negative association with the risk of developing valvular disease (OR = 0.98, 95% CI 0.95-1.00; P = 0.046) and hypertrophic cardiomyopathy (OR = 0.01, 95% CI 0.00-0.22; P = 0.016). Multiple test correction found that metformin treatment was causally associated with the risk of both hypertrophic cardiomyopathy (PFDR = 0.048) and myocardial infarction (PFDR = 0.012). The analysis revealed limited heterogeneity in the individual results, absence of pleiotropy evidence, and indications of stability in the findings. The MR study discovered from a genetic standpoint that metformin may lower the risk of hypertrophic cardiomyopathy and valvular heart disease, yet it could elevate the risk of myocardial infarction.

Impact of Wildfires on Cardiovascular Health.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

Personal Strategies to Reduce the Cardiovascular Impacts of Environmental Exposures.

Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality. Other evidence may support physical activity, dietary modification, omega-3 fatty acid supplementation, and indoor and in-vehicle air conditioning as viable strategies to minimize adverse health effects. There is currently insufficient data to recommend specific personal approaches to reduce the adverse cardiovascular effects of noise pollution. Public health advisories for periods of extreme heat or cold should be observed, with limited evidence supporting a warm ambient home temperature and physical activity as strategies to limit the cardiovascular harms of temperature extremes. Perfluoroalkyl and polyfluoroalkyl substance exposure can be reduced by avoiding contact with perfluoroalkyl and polyfluoroalkyl substance-containing materials; blood or plasma donation and cholestyramine may reduce total body stores of perfluoroalkyl and polyfluoroalkyl substances. However, the cardiovascular impact of these interventions has not been examined. Limited utilization of pesticides and safe handling during use should be encouraged. Finally, vasculotoxic metal exposure can be decreased by using portable air cleaners, home water filtration, and awareness of potential contaminants in ground spices. Chelation therapy reduces physiological stores of vasculotoxic metals and may be effective for the secondary prevention of cardiovascular disease.

Greenspaces And Cardiovascular Health.

Accumulating evidence suggests that living in areas of high surrounding greenness or even brief exposures to areas of high greenery is conducive to cardiovascular health, which may be related to the environmental, social, psychological, and physiological benefits of greenspaces. Recent data from multiple cross-sectional, longitudinal, and cohort studies suggest that living in areas of high surrounding greenness is associated with a lower risk of all-cause and cardiovascular mortality. High levels of neighborhood greenery have been linked also to a decrease in the burden of cardiovascular disease risk factors as reflected by lower rates of hypertension, dyslipidemia, and diabetes. Those who live in greener environments report better mental health and more frequent social interactions, which can benefit cardiovascular health as well. In this narrative review, we discuss evidence linking greenspaces to cardiovascular health as well as the potential mechanisms underlying the beneficial effects of greenspaces, including the impact of vegetation on air, noise and light pollution, ambient temperature, physical activity, mental health, and biodiversity. We review literature on the beneficial effects of acute and chronic exposure to nature on cardiovascular disease risk factors, inflammation and immune function, and we highlight the potential cardiovascular effects of biogenic volatile organic compounds that are emitted by trees and shrubs. We identify current knowledge gaps in this area and underscore the need for additional population studies to understand more clearly and precisely the link between greenness and health. Such understanding is urgently needed to fully redeem the promise of greenspaces in preventing adverse environmental exposures, mitigating the effects of climate change, and creating healthier living environments.

Are the cardiovascular properties of GLP-1 receptor agonists differentially modulated by sulfonylureas? Insights from post-hoc analysis of EXSCEL

AimsTo examine whether the cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are attenuated by concurrent sulfonylurea (SU) therapy in a post-hoc analysis of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). MethodsWe investigated whether SUs, as a class or by specific type, modulated the effects of once-weekly exenatide (EQW) on EXSCEL cardiovascular outcomes in intent-to-treat analyses of all trial participants, categorized as SU users or nonusers. Marginal structural models were used to evaluate whether there were differential EQW effects by SU category on major adverse cardiovascular events (MACE), depending on duration of SU use (6, 12, and 18 months). EQW-by-SU type interaction p-values and hazard ratios (95 % CIs) for EQW versus placebo for each baseline SU type (glibenclamide, gliclazide, glimepiride, other SUs) were calculated. ResultsNeither SU use nor baseline SU type modified the effect of EQW on time to MACE (pinteraction = 0.88 and 0.78, respectively), nor did individual SU types, including glibenclamide (a systemically wide-acting SU). ConclusionsSUs did not modulate the effect of EQW on cardiovascular outcomes, suggesting that SU treatment choices need not be altered to optimize the cardiovascular effects of GLP-1 receptor agonists in people with type 2 diabetes.

Selection of NSAIDs for rational pharmacotherapy of chronic musculoskeletal pain: a clinical pharmacologist's perspective

Chronic musculoskeletal pain (CMSP) is one of the most common pathological conditions that limits patients' physical activity and reduces their quality of life. The analgesic and anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) make them the basis of pharmacotherapy for patients with chronic conditions affecting various parts of the musculoskeletal system. The main target of NSAIDs, cyclooxygenase (COX), exists in the form of two main isoforms, COX-1 and COX-2, the inhibition of each of which leads to a cascade of reactions at the cellular and tissue level that can cause both targeted pharmacological effects and side effects. The diversity of the chemical structures of NSAIDs leads to differences in their pharmacodynamic and pharmacokinetic parameters and correspondingly to differences in their efficacy and safety profile. Selective COX-2 inhibitors, coxibs, have shown an increased risk of cardiovascular side effects, which has led to significant restrictions on their use. Cardiotoxicity is not as pronounced with the non-selective COX inhibitors, but the range of their side effects is extremely wide. These side effects are dose-dependent and are characteristic, first of all, of systemic NSAIDs.The combination of systemic and topical NSAIDs makes it possible to reduce the dose of the former and improve the safety profile of anti-inflammatory therapy. Among the non-selective COX inhibitors with a satisfactory safety profile and high anti-inflammatory activity, the group of oxicams and especially tenoxicam should be emphasised, which are characterised by a maximum duration of action, which is an advantage in the treatment of patients with CMSP. This review addresses the issues of rational selection of NSAIDs based on comparative data on pharmacodynamics, pharmacokinetics and clinical trial results.