Pubblicazioni recenti - cardiovascular risk
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Effectiveness and Cost-Effectiveness of Survivorship Care for Survivors of Hodgkin Lymphoma (INSIGHT Study): Protocol for a Multicenter Retrospective Cohort Study With a Quasi-Experimental Design.
JMIR Res Protoc2024 Apr;13():e55601. doi: 10.2196/55601.
Lammers Eline M J, Zijlstra Josée M, Retèl Valesca P, Aleman Berthe M P, van Leeuwen Flora E, Nijdam Annelies, ,
Abstract
BACKGROUND:
Hodgkin lymphoma (HL) occurs at young ages, with the highest incidence between 20 and 40 years. While cure rates have improved to 80%-90% over the past decades, survivors of HL are at substantial risk of late treatment-related complications, such as cardiovascular diseases, breast cancer, severe infections, and hypothyroidism. To reduce morbidity and mortality from late treatment effects, the Dutch Better care after lymphoma, Evaluation of long-term Treatment Effects and screening Recommendations (BETER) consortium developed a survivorship care program for 5-year survivors of HL that includes risk-based screening for and treatment of (risk factors for) late adverse events. Even though several cancer survivorship care programs have been established worldwide, there is a lack of knowledge about their effectiveness in clinical practice.
OBJECTIVE:
The Improving Nationwide Survivorship care Infrastructure and Guidelines after Hodgkin lymphoma Treatment (INSIGHT) study evaluates whether Dutch BETER survivorship care for survivors of HL decreases survivors' burden of disease from late adverse events after HL treatment and associated health care costs and improves their quality of life.
METHODS:
The INSIGHT study is a multicenter retrospective cohort study with a quasi-experimental design and prospective follow-up, embedded in the national BETER survivorship care infrastructure. The first BETER clinics started in 2013-2016 and several other centers started or will start BETER clinics in 2019-2024. This allows us to compare survivors who did and those who did not receive BETER survivorship care in the last decade. Survivors in the intervention group are matched to controls (n=450 per group) based on sex, age at diagnosis (±5 years), age in 2013 (±5 years), and treatment characteristics. The primary outcome is the burden of disease in disability-adjusted life years from cardiovascular disease, breast cancer, severe infections, and hypothyroidism. In a cost-effectiveness analysis, we will assess the cost of BETER survivorship care per averted or gained disability-adjusted life year and quality-adjusted life year. Secondary outcomes are BETER clinic attendance, adherence to screening guidelines, and knowledge and distress about late effects among survivors of HL. Study data are collected from a survivor survey, a general practitioner survey, medical records, and through linkages with national disease registries.
RESULTS:
The study was funded in November 2020 and approved by the institutional review board of the Netherlands Cancer Institute in July 2021. We expect to finalize recruitment by October 2024, data collection by early 2025, and data analysis by May 2025.
CONCLUSIONS:
INSIGHT is the first evaluation of a comprehensive survivorship program using real-world data; it will result in new information on the (cost-)effectiveness of survivorship care in survivors of HL in clinical practice. The results of this study will be used to improve the BETER program where necessary and contribute to more effective evidence-based long-term survivorship care for lymphoma survivors.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):
PRR1-10.2196/55601.
©Eline M J Lammers, Josée M Zijlstra, Valesca P Retèl, Berthe M P Aleman, Flora E van Leeuwen, Annelies Nijdam, BETER consortium. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.04.2024.
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Racial Discrimination and Metabolic Syndrome in Young Black Adults.
JAMA Netw Open2024 Apr;7(4):e245288. doi: 10.1001/jamanetworkopen.2024.5288.
Heard-Garris Nia, Yu Tianyi, Brody Gene, Chen Edith, Ehrlich Katherine B, Miller Gregory E,
Abstract
IMPORTANCE:
Metabolic syndrome (MetS) is a common health condition that predisposes individuals to cardiovascular disease (CVD) and disproportionately affects Black and other racially and ethnically minoritized people. Concurrently, Black individuals also report more exposure to racial discrimination compared with White individuals; however, the role of discrimination in the development of MetS over time and associated mediators in these pathways remain underexplored.
OBJECTIVE:
To evaluate the association between racial discrimination and MetS in rural Black individuals transitioning from late adolescence into early adulthood and to identify potential mediating pathways.
DESIGN, SETTING, AND PARTICIPANTS:
This longitudinal cohort study included Black adolescents enrolled in the Strong African American Families Healthy Adults (SHAPE) Project between June 2009 and May 2021. Families resided in rural counties of Georgia, where poverty rates are among the highest in the nation. Analyses included 322 of the 500 participants who originally enrolled in SHAPE and who were eligible to participate. Guardians provided information about socioeconomic disadvantage. Analyses were conducted in April 2023.
EXPOSURES:
Youths reported exposure to racial discrimination annually from ages 19 to 21 years.
MAIN OUTCOMES AND MEASURES:
MetS was the main health outcome and was measured at ages 25 and 31 years. MetS was diagnosed according to the International Diabetes Federation guidelines, which requires central adiposity (ie, waist circumference ?94 cm for males and ?80 cm for females) and at least 2 of the 4 additional components: signs of early hypertension (ie, systolic blood pressure ?130 mm Hg or diastolic blood pressure ?85 mm Hg); elevated triglyceride levels (ie, >150 mg/dL); elevated fasting glucose level (ie, ?100 mg/dL); or lowered high-density lipoprotein levels (ie,
RESULTS:
In 322 participants (210 [65.2%] female) ages 19 to 21 years, more frequent exposure to racial discrimination was associated with higher suPAR levels (b?=?0.006; 95% CI, 0.001-0.011; P?=?.01) and more sleep problems at age 25 years (b?=?0.062; 95% CI, 0.028-0.097; P?.001) as well as a 9.5% higher risk of MetS diagnosis at age 31 years (odds ratio [OR], 1.10; 95% CI, 1.01-1.20; P?=?.03). Both suPAR (b?=?0.015; 95% CI, 0.002-0.037) and sleep problems (b?=?0.020; 95% CI, 0.002-0.047) at age 25 years were significant indirect pathways. No significant interactions between sex and discrimination emerged.
CONCLUSIONS AND RELEVANCE:
This study suggests that racial discrimination in late adolescence is associated with MetS among Black young adults through biobehavioral pathways. Thus, health interventions for MetS in Black adults will need to contend with sleep behaviors and inflammatory intermediaries as well as address and reduce exposure to racial discrimination to narrow disparities and promote health equity.
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Age-related changes of interoceptive brain networks: Implications for interoception and alexithymia.
Emotion2024 Apr;():. doi: 10.1037/emo0001366.
Dobrushina Olga R, Dobrynina Larisa A, Arina Galina A, Pechenkova Ekaterina V, Kremneva Elena I, Gubanova Mariia V, Novikova Evgenia S, Kazantseva Daria A, Suslina Anastasia D, Krotenkova Marina V,
Abstract
Aging is known to be associated with a decline in interoceptive abilities and changes in emotional processing, including alexithymia. As the brain areas supporting interoceptive awareness participate in the perception of emotion, we suggested that interoceptive decline and alexithymia in older adults may share common neural ground. To test this hypothesis, we administered functional magnetic resonance imaging-based heartbeat detection task to 62 adults of diverse ages (range 18-73) and evaluated a larger sample of older and younger adults using questionnaires characterizing interoceptive sensibility, alexithymia, and depressive attitudes. We found that increasing age was linked to decreased activation during the interoceptive task, including the right insular-opercular and supplementary motor areas (SMAs). Age also affected task-based functional connectivity, with two major effects being a decrease in the connectivity of the SMA-insular network and an increase in the connectivity of the prefrontal-lateral occipital network. Path analysis performed for interoceptive accuracy as the endogenous variable revealed that the impact of age was mediated by the functional activation of the insular cortex and SMA and by the connectivity between these areas. Another path analysis using alexithymia as the endogenous variable while controlling for depressive attitudes showed that the effect of age was mediated by interoceptive decline. The study supports the role of central mechanisms in age-related interoceptive decline and shows its implications for alexithymia. Since alexithymia represents a risk factor for mental and cardiovascular diseases, the study findings may open an important direction toward maintaining older adults' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Associations between prenatal loss of control eating and cardiovascular health during pregnancy.
Health Psychol2024 Apr;():. doi: 10.1037/hea0001392.
Jouppi Riley J, Donofry Shannon D, Call Christine C, Cheng Yu, Conlon Rachel P Kolko, Niemi Sarah, Levine Michele D,
Abstract
OBJECTIVE:
Loss of control (LOC) eating (feeling unable to control food type/amount eaten) during pregnancy is common and linked to risk for poor cardiovascular health (CVH), but it is unclear whether prenatal LOC eating directly relates to CVH during pregnancy. The current study tested associations between prenatal LOC eating and CVH during pregnancy in a sample with prepregnancy body mass index (BMI) ? 25.
METHOD:
At 12-20 weeks' gestation, participants ( = 124) self-reported: prenatal LOC eating, diet, physical activity, nicotine use, sleep; height/weight were measured. Data were collected during 2015-2017. We dichotomized LOC eating (0 = ; 1 = ) and scored CVH metrics using Life's Essential 8 to create a composite CVH score (range = 0-100; higher = better). Linear and binary logistic regression models tested if LOC eating is related to composite CVH score and odds of scoring (0)/ (1) on each CVH metric, respectively. All models employed propensity score adjustment, since those with/without LOC eating may differ in ways affecting CVH, and covaried for: age, gestational age, prepregnancy BMI, ethnicity, race, education, and income.
RESULTS:
Compared to those without, participants with LOC eating had significantly poorer composite CVH scores ( = -9.27, (111) = -2.70,
CONCLUSIONS:
Prenatal LOC eating was associated with poorer CVH during pregnancy in this sample with prepregnancy BMI ? 25, even after controlling for propensity of experiencing LOC eating and known risk factors for poor CVH. Thus, prenatal LOC may represent a modifiable factor related to prenatal health risk. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm.
Clin Res Cardiol2024 Apr;():. doi: 10.1007/s00392-024-02446-x.
Tremmel Roman, Martínez Pereyra Valeria, Broders Incifer, Schaeffeler Elke, Hoffmann Per, Nöthen Markus M, Bekeredjian Raffi, Sechtem Udo, Schwab Matthias, Ong Peter,
Abstract
BACKGROUND:
Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic variants in a cohort of European patients with angina and unobstructed coronary arteries who underwent acetylcholine (ACh) provocation testing.
METHODS:
A candidate association analysis of 208 genes previously associated with cardiovascular conditions was performed using genotyped and imputed variants in patients grouped in epicardial (focal, diffuse) CAS (n?=?119) and microvascular CAS (n?=?87). Patients with a negative ACh test result (n?=?45) served as controls.
RESULTS:
We found no association below the genome-wide significance threshold of p?5?×?10, thus not confirming variants in ALDH2, NOS3, and ROCK2 previously reported in CAS patients of Asian ancestry. However, the analysis identified suggestive associations (p?10) for the groups of focal epicardial CAS (CDH13) and diffuse epicardial CAS (HDAC9, EDN1). Downstream analysis of the potential EDN1 risk locus showed that CAS patients have significantly increased plasma endothelin-1 levels (ET-1) compared to controls. An EDN1 haplotype comprising rs9349379 and rs2070698 was significantly associated to ET-1 levels (p?=?0.01).
CONCLUSIONS:
In summary, we suggest EDN1 as potential genetic risk loci for patients with diffuse epicardial CAS, and European ancestry. Plasma ET-1 levels may serve as a potential cardiac marker.
© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.
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Assessment of ICD eligibility in non-ischaemic cardiomyopathy patients: a position statement by the Task Force of the Dutch Society of Cardiology.
Neth Heart J2024 Apr;():. doi: 10.1007/s12471-024-01859-7.
van der Lingen Anne-Lotte C J, Verstraelen Tom E, van Erven Lieselot, Meeder Joan G, Theuns Dominic A, Vernooy Kevin, Wilde Arthur A M, Maass Alexander H, Allaart Cornelis P,
Abstract
International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with a left ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and a life expectancy of more than 1 year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides a more careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.
© 2024. The Author(s).
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Safety of Linagliptin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials.
Ther Innov Regul Sci2024 Apr;():. doi: 10.1007/s43441-024-00637-2.
Aljohani Hadir, Alrubaish Fares S, Alghamdi Waad M, Al-Harbi Fawaz,
Abstract
BACKGROUND:
Linagliptin is an oral dipeptidyl peptidase DPP-4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy with other hypoglycemic drugs.
OBJECTIVES:
We aimed to summarize the evidence from randomized controlled trials (RCTs) to assess the safety of linagliptin focusing on cardiovascular risks among subjects with type 2 diabetes mellitus.
METHODS:
We conducted a systematic search across the following databases: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to November 2021. Randomized controlled trials (RCTs) of linagliptin compared to placebo in patients with Type 2 diabetes were included. The primary safety points were cardiovascular (CV) adverse events including non-fatal stroke, non-fatal myocardial infarction (MI), CV death, MI, stroke, and hospitalization for unstable angina. While, secondary safety points included 17 reported adverse events such as infections, hypoglycemia and abdominal pain. Three reviewers independently screened and reviewed each study to extract relevant information. Any discrepancies were resolved by consensus. We conducted a meta-analysis using the random effects model. Pooled risk ratios (RRs) of targeted adverse events with linagliptin compared to placebo were estimated using the Mantel-Haenszel test.
RESULTS:
A total of 24 studies with 19,981 adult patients were included. There was no difference in the incidence of all CV adverse events or individual CV adverse events between linagliptin and the placebo arms. The pooled estimate of the risk of upper respiratory tract infection was reported in twelve trials with a 38% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR?=?0.62, 95% CI: 0.45-0.85, and I?=?0%), while no difference was found in other infections. For gastrointestinal disorders, the risk of abdominal pain showed a 65% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR?=?0.35, 95% CI: 0.16-0.77, and I?=?0%).
CONCLUSION:
Our study showed an overall acceptable safety profile of linagliptin in patients with T2DM. Moreover, our study showed a risk reduction of upper respiratory tract infection and abdominal pain when using linagliptin compared to placebo.
© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.
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Unexplained Residual Risk In Type 2 Diabetes: How Big Is The Problem?
Curr Cardiol Rep2024 Apr;():. doi: 10.1007/s11886-024-02055-0.
Neppala Sivaram, Rajan Jemema, Yang Eric, DeFronzo Ralph A,
Abstract
PURPOSE OF REVIEW:
What is new? Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes (T2D) individuals. Of the major risk factors for CVD, less than 10% of T2D people meet the American Diabetes Association/American Heart Association recommended goals of therapy. The present review examines how much of the absolute cardiovascular (CV) risk in type 2 diabetes patients can be explained by major CV intervention trials.
RECENT FINDINGS:
Multiple long-term cardiovascular (CV) intervention trials have examined the effect of specific target-directed therapies on the MACE endpoint. Only one prospective study, STENO-2, has employed a multifactorial intervention comparing intensified versus conventional treatment of modifiable risk factors in T2D patients, and demonstrated a 20% absolute CV risk reduction. If the absolute CV risk reduction in these trials is added to that in the only prospective multifactorial intervention trial (STENO-2), the unexplained CV risk is 44.1%. What are the clinical implications? Potential explanations for the unaccounted-for reduction in absolute CV risk in type 2 diabetes (T2D) patients are discussed.
HYPOTHESIS:
failure to take into account synergistic interactions between major cardiovascular risk factors is responsible for the unexplained CV risk in T2D patients. Simultaneous treatment of all major CV risk factors to recommended AHA/ADA guideline goals is required to achieve the maximum reduction in CV risk.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Health and economic impact of dapagliflozin for type 2 diabetes patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian general practitioners setting: a budget impact analysis.
Acta Diabetol2024 Apr;():. doi: 10.1007/s00592-024-02276-3.
Cortesi Paolo Angelo, Antonazzo Ippazio Cosimo, Palladino Pasquale, Gnesi Marco, Mele Silvia, D'Amelio Marco, Zanzottera Ferrari Elena, Mazzaglia Giampiero, Mantovani Lorenzo Giovanni,
Abstract
AIM:
In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting.
METHODS:
A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact.
RESULTS:
The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305?: 14,521,464? in the first year, 33,007,064? in the second and 55,163,777? in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potentially eligible to the treatment were the factor with largest impact on the results.
CONCLUSIONS:
The use of dapagliflozin in GPs setting reduce the number of CVD events, kidney disease progression and healthcare costs in Italy. These data should be considered to optimize the value produced for the T2D patients who had or were at risk for atherosclerotic cardiovascular disease.
© 2024. The Author(s).
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The relevance of intestinal barrier dysfunction, antimicrobial proteins and bacterial endotoxin in metabolic dysfunction-associated steatotic liver disease.
Eur J Clin Invest2024 Apr;():e14224. doi: 10.1111/eci.14224.
Bergheim Ina, Moreno-Navarrete José María,
Abstract
BACKGROUND:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of end-stage liver disease associated with increased mortality and cardiovascular disease. Obesity and diabetes are the most important risk factors of MASLD. It is well-established that obesity-associated insulin resistance leads to a situation of tissue lipotoxicity characterized by an accumulation of excess fat in non-fat tissues such as the liver, promoting the development of MASLD, and its progression into metabolic dysfunction-associated steatohepatitis.
METHODS:
Here, we aimed to review the impact of disrupted intestinal permeability, antimicrobial proteins and bacterial endotoxin in the development and progression of MASLD.
RESULTS AND CONCLUSION:
Recent studies demonstrated that obesity- and obesogenic diets-associated alterations of intestinal microbiota along with the disruption of intestinal barrier integrity, the alteration in antimicrobial proteins and, in consequence, an enhanced translocation of bacterial endotoxin into bloodstream might contribute to this pathological process through to impacting liver metabolism and inflammation.
© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.
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Editorial comments: focus on cardiovascular risk estimation and prevention.
Eur J Prev Cardiol2024 Apr;31(6):641-643. doi: 10.1093/eurjpc/zwae122.
Guida Gianluigi, Attanasio Andrea, Disabato Giandomenico, Piepoli Massimo,
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Gliflozins in the Treatment of Non-diabetic Experimental Cardiovascular Diseases.
Physiol Res2024 Apr;():.
Van??ková I, Zicha J,
Abstract
A new class of antidiabetic drugs - gliflozins (inhibitors of sodium glucose cotransporter-2; SGLT-2i) stimulate glucose and sodium excretion, thereby contributing to improved glycemic control, weight loss and blood pressure reduction in diabetic patients. Large clinical trials in patients with type 2 diabetes treated with empagliflozin, canagliflozin or dapagliflozin have demonstrated their excellent efficacy in improving many cardiovascular outcomes, including the reduction of death from cardiovascular diseases, non-fatal myocardial infarction or stroke, and hospitalization for heart failure. Moreover, the beneficial effects of SGLT-2i were also demonstrated in the decrease in proteinuria, which leads to a lower risk of progression to end-stage renal disease and thus a delay in initiation of the renal replacement therapy. Unexpectedly, their cardioprotective and renoprotective effects have been demonstrated not only in patients with diabetes but also in those without diabetes. Recently, much effort has been focused on patients with heart failure (either with reduced or preserved ejection fraction) or liver disease. Experimental studies have highlighted pleiotropic effects of SGLT-2 inhibitors beyond their natriuretic and glycosuric effects, including reduction of fibrosis, inflammation, reactive oxygen species, and others. Our results in experimental non-diabetic models of hypertension, chronic kidney disease and heart failure are partially consistent with these findings. This raises the question of whether the same mechanisms are at work in diabetic and non-diabetic conditions, and which mechanisms are responsible for the beneficial effects of gliflozins under non-diabetic conditions. Are these effects cardio-renal, metabolic, or others? This review will focus on the effects of gliflozins under different pathophysiological conditions, namely in hypertension, chronic kidney disease, and heart failure, which have been evaluated in non-diabetic rat models of these diseases. Key words: SGLT-2 inhibitor, hypertension, chronic kidney disease, heart failure, liver disease, rat.
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Circadian Disruption as a Risk Factor for Development of Cardiovascular and Metabolic Disorders - From Animal Models to Human Population.
Physiol Res2024 Apr;():.
Sumová A, Sládek M,
Abstract
The lifestyle of human society is drifting apart from the natural environmental cycles that have influenced it since its inception. These cycles were fundamental in structuring the daily lives of people in the pre-industrial era, whether they were seasonal or daily. Factors that disrupt the regularity of human behaviour and its alignment with solar cycles, such as late night activities accompanied with food intake, greatly disturb the internal temporal organization in the body. This is believed to contribute to the rise of the so-called diseases of civilization. In this review, we discuss the connection between misalignment in daily (circadian) regulation and its impact on health, with a focus on cardiovascular and metabolic disorders. Our aim is to review selected relevant research findings from laboratory and human studies to assess the extent of evidence for causality between circadian clock disruption and pathology. Keywords: Circadian clock, Chronodisruption, Metabolism, Cardiovascular disorders, Spontaneously hypertensive rat, Human, Social jetlag, Chronotype.
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Inflammatory, Metabolic and Endothelial Biomarkers Before and After Pregnancy Complications.
Am J Epidemiol2024 Apr;():. doi: kwae053.
Sun Baiyang, Gunderson Erica P, Bertolet Marnie, Lopa Samia H, Bryan Samantha G, Lewis Cora E, Catov Janet M,
Abstract
Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared to those with uncomplicated births, perhaps related to pre-pregnancy inflammation, dysmetabolism or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Repeated measures ANOVA estimated pre-pregnancy, post-pregnancy and biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and HDP groups had higher pre-pregnancy hsCRP (+0.37 [0.08, 0.65]; +0.29 [0.04, 0.55] log mg/L), leptin (+0.29 [0.09, 0.50]; +0.37 [0.17, 0.56] log ng/ml), and lower adiponectin (-0.25 [-0.36, -0.13); -0.11 [-0.22, -0.01] log ng/ml) than those with uncomplicated births and these profiles persisted in magnitude post-pregnancy. Controlling for BMI attenuated most profiles, except lower pre-pregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower pre-pregnancy hsCRP and sICAM-1 (-0.31 [-0.56, -0.06] log mg/L; -0.05 [-0.09, - 0.01] log ng/ml) and a larger leptin increase from pre- to post-pregnancy, (+0.20 [0.02, 0.37] log ng/ml). Pre-pregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher BMI. PTB may be related to adverse metabolic changes post-pregnancy, though the unexpected endothelial biomarker profile warrants further study.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Mannose Binding Lectin and C3 Serum Levels in Coronary Artery Disease: A Cross-Sectional Study.
Immunol Invest2024 Apr;():1-14. doi: 10.1080/08820139.2024.2337023.
Meneghetti da Rosa Juliana, Lidani Kárita Cláudia Freitas, Andrade Fabiana Antunes, Sena Léia, Nisihara Renato, Ambrosio Altair Rogerio, Messias-Reason Iara J,
Abstract
BACKGROUND:
The process of tissue injury in coronary artery disease (CAD) has been associated with activation of the complement system, partly due to the action of mannose-binding lectin (MBL) and C3, which are expressed in atherosclerotic lesions.
OBJECTIVE:
The aim of this study was to evaluate the serum levels of MBL and C3 in patients with CAD and to compare them with healthy controls. Additionally, we aim to assess the correlation between MBL and C3 levels and cardiometabolic parameters.
METHODS:
MBL and C3 serum concentration were determined by ELISA and immunoturbidimetry, respectively, in up to 119 patients undergoing coronary angiography for CAD evaluation, comprising 48 individuals diagnosed with acute myocardial infarction (MI) and 71 without MI. A total of 93 paired healthy controls were included in the study.
RESULTS:
Individuals with CAD had MBL serum concentration higher than controls (?=?.002), regardless of the presence of MI (?=?.006). In addition, high concentration of MBL (>2000?ng/mL) was more frequent in patients with CAD (?=?.007; OR?=?2.6; 95% CI?=?1.3-5.1). C3 levels were not significantly associated with any of the patient groups but were positively correlated with cardiometabolic parameters such as body mass index (BMI) and triglycerides levels.
CONCLUSIONS:
Higher concentrations of MBL were found to be associated with CAD, whereas C3 levels were found to be associated with cardiovascular risk factors.
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Identifying Vulnerabilities to NSAID Adverse Events in the U.S. Population: An Analysis of Preexisting Conditions and Sex.
J Womens Health (Larchmt)2024 Apr;():. doi: 10.1089/jwh.2023.1039.
Rogers Paul, Wang Dong, Lu Zhiyuan, Lyn-Cook Beverly,
Abstract
In 2005, the Food and Drug Administration (FDA) issued a decision memorandum regarding nonsteroidal anti-inflammatory drugs (NSAIDs). The memorandum recommended the withdrawal of certain NSAIDs due to potential cardiovascular adverse effects. It highlighted the issue of cardiovascular risk associated with NSAIDs as a class. The NSAID medication guide includes a wide range of adverse drug reactions (ADRs), such as increased blood pressure, liver failure, allergic reactions, heart attack, and intestinal bleeding. Although both sexes have an increased risk of ADRs with NSAID use, females have a greater risk than males due to differences in pharmacodynamics and higher medication concentrations (mg/kg). In particular, females with high blood pressure, coronary heart, kidney, and liver disease are at an additional risk of harm from NSAID ADRs. This study quantifies sex-specific differences and other factors associated with prescription NSAID use. The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), a complex survey conducted by the Centers for Disease Control and Prevention (CDC) in two-year cycles. A survey-weighted logistic regression model was utilized to investigate potential sex differences with prescription NSAIDs in the context of other factors, including kidney disease, hypertension, liver disease, insurance status, coronary heart disease, and age, within the 2011-2018 NHANES survey data. Females reported a slightly higher percentage of high blood pressure and kidney disease than males, while males reported a slightly higher percentage of coronary heart and liver disease than females. Last, the model indicated that females were 58% more likely to have used a prescription NSAID than males. The results confirm that women and people with medical conditions, who would potentially suffer greater harm from NSAID ADRs, are more likely to use a prescription NSAID than individuals without these conditions.
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An Enhanced Postpartum Transition Program to Primary Care.
J Womens Health (Larchmt)2024 Apr;():. doi: 10.1089/jwh.2023.0465.
Cameron Natalie A, Birdsell Heather, Niznik Charlotte M, Michon Ruth, Donelan Emily, Yee Lynn M, Dolan Brigid M,
Abstract
Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are risk factors for future cardiovascular disease, yet few individuals receive postpartum care with primary care clinicians (PCP). To facilitate transitions of care to PCPs and improve cardiovascular health monitoring within the first 13 months postpartum, we developed and piloted an enhanced postpartum referral pathway for patients with GDM or HDP. Eligible patients included those who received perinatal care at a large, urban, academic medical center, experienced GDM or HDP during their most recent pregnancy, and lacked an existing PCP. Resident, faculty, and advanced practitioners referred patients during antenatal, delivery-related, or postpartum visits. A dedicated scheduler contacted patients to schedule an appointment with a women's health-focused resident or faculty PCP. The percent of patients who attended a postpartum PCP visit, who had an HbA1c and cholesterol panel checked within the first 13 months postpartum, were compared between patients referred and not referred to the program using adjusted odds ratios (aOR). Of 129 individuals referred, 48.1% attended a PCP visit, 31.8% completed cholesterol screening, and 41.9% completed HbA1c screening within 13 months postpartum. After adjusting for age, parity, insurance, and referral indication, referred individuals had greater odds for each outcome (PCP visit: aOR = 6.0, 95% CI 4.0-9.0; cholesterol: aOR = 2.4, 95% 1.6-3.9; HbA1c: aOR = 2.5, 95% CI 1.7-3.7) compared with nonreferred individuals in the same time period. A enhanced postpartum PCP referral pathway pilot for birthing individuals was associated with improved follow-up in the first year postpartum.
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Age-specific sex-differences in cerebral blood flow velocity in relation to haemoglobin levels.
Eur Stroke J2024 Apr;():23969873241245631. doi: 10.1177/23969873241245631.
Mazzucco Sara, Li Linxin, Tuna Maria Assuncao, Rothwell Peter M,
Abstract
INTRODUCTION:
Cerebral blood flow (CBF) declines with age and abnormalities in CBF are associated with age-related cerebrovascular disease and neurodegeneration. Women have higher CBF than men, although this sex-difference diminishes to some extent with age in healthy subjects. The physiological drivers of these age/sex differences are uncertain, but might be secondary to age and sex-differences in haemoglobin (Hb) level. Hb levels are inversely correlated with CBF, are lower in women, and decline with age in men, but the interrelations between these factors have not been explored systematically either in healthy subjects or across the full age-range in patients with vascular risk factors. We aimed to determine the age-specific interrelations between sex, Hb, and CBF velocity in a large cohort of patients with cerebrovascular disease.
PATIENTS AND METHODS:
In patients with a recent transient ischaemic attack or minor stroke (Oxford Vascular Study) and no ipsilateral or contralateral stenosis of the carotid or intracranial arteries, we related peak-systolic velocity (PSV) and other parameters on transcranial Doppler ultrasound (TCD) of the middle cerebral artery to sex, age, Hb and vascular risk factors.
RESULTS:
Of 958 eligible subjects (mean age/SD?=?68.04/14.26, 53.2% male), younger women (age?55?years) had higher CBF velocities than men (mean sex difference in PSV at age?55 years?=?16.31?cm/s; ?0.001), but this difference declined with age (interaction ?0.001), such that it was no longer significant at age 75-84 (?PSV?=?3.26?cm/s; ?=?0.12) and was reversed at age???85 (?PSV?=?-7.42?cm/s; ?=?0.05). These changes mirrored trends in levels of Hb, which were higher in men at age?55 (?Hb?=?1.92?g/dL; ?0.001), but steadily decreased with age in men but not in women (interaction ?0.001), with no residual sex-difference at age???85 (?Hb?=?0.12?g/dL; ?=?0.70). There was an inverse correlation between Hb and PSV in both women and men (both ???0.01), and the sex-difference in PSV at age?55 was substantially diminished after adjustment for Hb (?PSV?=?6.92; ?=?0.036; ?PSV?=?5.92, ?=?0.13 with further adjustment for end-tidal CO). In contrast, the sex difference in PSV was unaffected by adjustment for systolic and diastolic blood pressure, heart rate, and vascular risk factors (history of hypertension, diabetes, hyperlipidaemia and smoking).
DISCUSSION:
CBF velocity is strongly correlated with Hb level at all ages, and sex-differences in CBF velocity appear to be explained in major part by age-related sex-differences in Hb.
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Association of Interhospital Transfer With Outcomes of Extracorporeal Membrane Oxygenation: A Contemporary Analysis.
Am Surg2024 Apr;():31348241248699. doi: 10.1177/00031348241248699.
Balian Jeffrey, Mallick Saad, Le Nguyen, Porter Giselle, Vadlakonda Amulya, Ali Konmal, Kronen Elsa, Benharash Peyman,
Abstract
BACKGROUND:
Extracorporeal membrane oxygenation (ECMO) has emerged as a life-sustaining measure for individuals with end-stage cardiopulmonary derangements. An estimated one-third of patients must be transferred to a specialized center to receive this intervention. Therefore, the present study sought to characterize the impact of interhospital transfer (IHT) status on outcomes following ECMO.
METHODS:
The 2016-2020 National Inpatient Sample was queried to identify all adult (?18 years) hospitalizations for ECMO. Patients were stratified based on transfer status from another acute care hospital. Multivariable regression models were developed to assess the association between transfer status and outcomes of interest. Patient and operative factors associated with IHT were identified using regression.
RESULTS:
Of an estimated 61,180 hospitalizations entailing ECMO, 21,410 (35.0%) were transfers. Annual transfer volume doubled over the study period, from 2915 to 5945 (nptrend
CONCLUSION:
Despite increasing transfer volume and utilization of ECMO, IHT was associated with significant mortality and hospital complication risks. Further work to reduce adverse outcomes, resource burden, and socioeconomic differences within IHT may improve accessibility to this life-saving modality.
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Polymorphisms in and associated with dry mouth in clozapine-treated patients.
Acta Neuropsychiatr2024 Apr;():1-19. doi: 10.1017/neu.2024.9.
Puolakka Hanna, Solismaa Anssi, Lyytikäinen Leo-Pekka, Viikki Merja, Seppälä Niko, Mononen Nina, Lehtimäki Terho, Kampman Olli,
Abstract
OBJECTIVE:
Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes.
METHODS:
The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients.
RESULTS:
Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p=0.013) and use of other antipsychotics (p=0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: () rs3942465 (adjusted p=0.025) rs58933792 (adjusted p=0.029).
CONCLUSION:
Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in and might contribute to experienced dryness of mouth among patients treated with clozapine.
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