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Despite the predisposition to bleeding, patients with immune thrombocytopenia (ITP) may also have an increased risk of arterial and venous thrombosis, which can contribute to significant morbidity. The risk of thrombosis increases with age and the presence of cardiovascular risk factors. This narrative review explores the multifactorial nature of thrombosis in ITP, focusing on new pathological mechanisms, emerging evidence on the association between established treatments and thrombotic risk, the role of novel treatment approaches, and the challenges in assessing the balance between bleeding and thrombosis in ITP. The review also explores the challenges in managing acute thrombotic events in ITP, since the platelet count does not always reliably predict either the risk of bleeding or thrombosis and antithrombotic strategies lack specific guidelines for ITP. Notably, second-line therapeutic options, such as splenectomy and thrombopoietin receptor agonists (TPO-RAs), exhibit an increased risk of thrombosis especially in older individuals or those with multiple thrombotic risk factors or previous thrombosis, emphasizing the importance of careful risk assessment before treatment selection. In this context, it is important to consider second-line therapies such as rituximab and other immunosuppressive agents, dapsone and fostamatinib, which are not associated with increased thrombotic risk. In particular, fostamatinib, an oral spleen tyrosine kinase inhibitor, has promisingly low thrombotic risk. During the current era of the emergence of several novel ITP therapies that do not pose additional risks for thrombosis, it is critical to outline evidence-based strategies for the prevention and treatment of thrombosis in ITP patients.

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O diabetes mellitus tipo 2 (DM2) é uma doença que apresenta mecanismos fisiopatológicos multifatoriais e complexos, tendo como base a resistência insulínica (RI) e como consequências as doenças cardiovasculares (DCV). A hipomagnesemia tem sido implicada tanto na RI como em complicações micro e macrovasculares, incluindo-se as DCV que são consideradas a causa mais importante de morbimortalidade no DM2. Neste contexto, o presente estudo visa avaliar níveis séricos de magnésio (Mg) em pacientes diabéticos e sua possível associação com complicações crônicas e comorbidades, tendo como ênfase as doenças cardiovasculares; e identificar possível valor do nível sérico a ser considerado em nossa população a fim de rever sua verdadeira aplicabilidade clínica. Trata-se de estudo transversal, descritivo e analítico, envolvendo 99 pacientes com DM2 de ambos os sexos, atendidos em ambulatório público na cidade de Salvador (BA). Utilizou-se como instrumentos de pesquisa questionário de dados sociodemográficos e antropométricos; recordatório alimentar de 24 horas e análise bioquímica do magnésio sérico. Também foram registradas comorbidades e complicações crônicas dos pacientes, tais como hipertensão arterial, doença arterial coronariana, doença arterial obstrutiva periférica, arritmia cardíaca, acidente vascular cerebral, dislipidemia, neuropatia sensitiva periférica, retinopatia e nefropatia diabéticas. Os dados foram expressos por tabelas de forma descritiva e analítica. Os indivíduos foram divididos em dois grupos, magnésio baixo e normal/alto, e suas variáveis foram comparadas por meio de testes de hipóteses. Nossos achados evidenciaram nível sérico médio de magnésio de 1,97 mg% (IC 1,69 a 2,25 mg%) no total da amostra. Entre aqueles com magnésio baixo, níveis subclínicos estavam presentes em 29 sujeitos (29,3%), e níveis de hipomagnesemia em 34 indivíduos (34,3%). O nível médio do Mg no total da amostra diferiu significativamente (p<0,001) do valor normal ideal, mas não diferiu do considerado subclínico (p 0,311). No grupo com hipomagnesemia houve predomínio do sexo feminino e de pacientes com maior escolaridade. Glicemia de jejum foi mais elevada no grupo Mg baixo, e hemoglobina glicada no grupo Mg normal/alto, mas ambos sem diferença estatística. Níveis baixos de vitamina B12 foram encontrados em 12 pacientes (12,1%) e os níveis mais baixos de magnésio estavam presentes nos pacientes com deficiência de vitamina B12 (1,81±0,24 versus 2,01±0,29) com p=0,027. Antidiabéticos orais foram mais utilizados no grupo com Mg baixo. Não houve diferença entre magnésio sérico, ingestão calórica e magnésio e cálcio alimentares. Pacientes com DCV tiveram média de 2,01 mg% (IC 1,69-2,33 mg%) para o Mg. A doença cardiovascular esteve presente em 47,5% da amostra e pacientes com esta morbidade apresentaram 29,8% de prevalência de hipomagnesemia; infarto agudo do miocárdio (IAM) foi mais frequente no grupo com Mg normal/alto. Nossos dados apontam que hipomagnesemia em pacientes diabéticos deve ser considerada em níveis clínicos e subclínicos. Níveis baixos de Mg também estiveram associados à vitamina B12 baixa. Pacientes que apresentaram doenças cardiovasculares associadas também tiveram importante prevalência de hipomagnesemia incluindo níveis subclínicos, com exceção nos casos de IAM, em que níveis do magnésio sérico mantiveram-se no intervalo considerado normal ideal evidenciado por significativa diferença estatística (p<0,005).

Diabetes mellitus type 2 (DM2) is a multifactorial disease with complex physiopathological mechanisms, in which insulin resistance (IR) and its consequences, such as cardiovascular diseases (CVD), form its basis. Hypomagnesemia has been implicated in IR and micro and macrovascular complications, including CVD, which is considered the most important cause of morbidity and mortality in DM2. This study aims to evaluate serum magnesium (Mg) levels in diabetic patients and its possible association with chronic complications and comorbidities (especially cardiovascular diseases) and to find a possible serum level value to be considered in its population to review its true clinical applicability. This cross-sectional, descriptive, and analytical study involved 99 DM2 patients of all sexes who were served in a public outpatient clinic in Salvador-Ba. A sociodemographic and anthropometric data questionnaire, a 24-hour food recall, and serum magnesium analysis were used as research instruments. The comorbidities and chronic complications of patients, such as hypertension, coronary artery disease, peripheral arterial obstructive disease, cardiac arrhythmia, cerebrovascular accident, dyslipidemia, peripheral sensory neuropathy, diabetic retinopathy, and nephropathy, were also recorded. The data were expressed in descriptive and analytical tables. The individuals were divided into two groups, low and normal/high magnesium, and their variables were compared using hypothesis tests. Our findings showed an average serum magnesium level of 1.97 mg% (IC 1.69 to 2.25 mg%) in the whole sample. In those with low magnesium, subclinical levels occurred in 29 subjects (29.3%)and hypomagnesemia, in 34 individuals (34.3%). The median Mg level in the total sample significantly differed (p<0.001) from the ideal normal value, but failed to do in relation to the subclinical value (p=0.311). The hypomagnesemia group showed a predominance of women and patients with higher education. Fasting glucose was higher in the low Mg group and glycated hemoglobin in the normal/high Mg group, both without statistical differences. Low levels of vitamin B12 occurred in 12 patients (12.1%) and the lowest magnesium levels, in patients with vitamin B12 deficiency (1.81±0.24 versus 2.01±0.29) (p=0.027). Oral antidiabetics were more used in the group with low Mg. Serum magnesium, caloric intake, and dietetic magnesium and calcium showed no differences. Patients with CVD had an Mg average of 2.01 mg% (IC 1.69-2.33 mg%). Cardiovascular disease occurred in 47.5% of the sample. Patients with this morbidity had a 29.8% prevalence of hypomagnesemia. Moreover, myocardial infarction occurred more often in the normal/high Mg group. Data suggest that hypomagnesemia in diabetic patients should be considered at clinical and subclinical levels. Low Mg levels were also associated with low vitamin B12. Patients who showed cardiovascular diseases also had a high prevalence of hypomagnesemia, including subclinical levels, except in cases of myocardial infarction, in which serum magnesium levels remained within the normal ideal range, as evinced by its significant statistical difference (p<0.005).

La diabetes mellitus tipo 2 (DM2) es una enfermedad con mecanismos fisiopatológicos multifactoriales y complejos caracterizada por la resistencia a la insulina (RI) y sus consecuencias, como las enfermedades cardiovasculares (ECV). La hipomagnesemia está asociada con la RI y las complicaciones micro y macrovasculares, incluyendo las ECV, que se consideran la principal causa de morbimortalidad por la DM2. En este contexto, este estudio tiene como objetivo evaluar los niveles séricos de magnesio (Mg) en pacientes diabéticos y la posible asociación con complicaciones crónicas y comorbilidades, con énfasis en las enfermedades cardiovasculares; e identificar un posible valor de nivel sérico para considerar en esta población con el fin de revisar su verdadera aplicabilidad clínica. Se trata de un estudio transversal, descriptivo y analítico, en el cual participaron 99 pacientes con DM2 de ambos sexos, atendidos en un centro ambulatorio público en la ciudad de Salvador (Bahía, Brasil). Se utilizaron un cuestionario de datos sociodemográficos y antropométricos, un recordatorio alimentario de 24 horas y un análisis bioquímico del magnesio sérico. También se registraron las comorbilidades y complicaciones crónicas de los pacientes, como hipertensión arterial, enfermedad arterial coronaria, enfermedad arterial obstructiva periférica, arritmia cardíaca, accidente cerebrovascular, dislipidemia, neuropatía sensorial periférica, retinopatía y nefropatía diabética. Los datos se dispusieron en tablas para su análisis y descripción. Los individuos se separaron en dos grupos: bajo magnesio y normal/alto magnesio, y se compararon sus variables mediante pruebas de hipótesis. Los hallazgos evidenciaron un nivel sérico medio de magnesio de 1,97 mg% (IC 1,69 a 2,25 mg%) en el total de la muestra. Los bajos niveles subclínicos de magnesio estaban presentes en 29 sujetos (29,3%), y la hipomagnesemia en 34 individuos (34,3%). El nivel medio de Mg en el total de la muestra tuvo una diferencia significativa (p<0,001) del valor normal ideal, pero no difirió del valor subclínico (p=0,311). En el grupo con hipomagnesemia hubo predominio del sexo femenino y de pacientes con mayor nivel de estudios. La glucemia en ayunas fue más alta en el grupo de bajo Mg, y la hemoglobina glucosilada en el grupo de normal/alto Mg, pero en ninguno de los dos se encontró diferencia estadística. Los bajos niveles de vitamina B12 se encontraron en 12 pacientes (12,1%), y los niveles más bajos de magnesio estaban presentes en los pacientes con deficiencia de vitamina B12 (1,81±0,24 versus 2,01±0,29) con p=0,027. Los antidiabéticos orales se utilizaron más en el grupo con bajo Mg. No hubo diferencia entre el magnesio sérico, la ingesta calórica, el magnesio y el calcio en la dieta. Los pacientes con ECV tuvieron una media de 2,01 mg% (IC 1,69-2,33 mg%) para Mg. La enfermedad cardiovascular estuvo presente en el 47,5% de la muestra, y los pacientes con esta morbilidad tuvieron una prevalencia del 29,8% de hipomagnesemia; el infarto agudo de miocardio (IAM) fue más frecuente en el grupo con normal/alto Mg. Los resultados demuestran que la hipomagnesemia en los pacientes diabéticos debe considerarse en los niveles clínicos y subclínicos. Los bajos niveles de Mg también estuvieron asociados a bajos niveles de vitamina B12. Los pacientes que presentaron enfermedades cardiovasculares asociadas también tuvieron una alta prevalencia de hipomagnesemia, incluidos los niveles subclínicos, con excepción de los casos de IAM en los que los niveles séricos de magnesio se mantuvieron dentro del intervalo considerado normal ideal, evidenciado por una diferencia estadísticamente significativa (p<0,005).

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BACKGROUND AND AIMS: Understanding the amounts of intensity-specific movement needed to attenuate the association between sedentary time and mortality may help to inform personalized prescription and behavioral counselling. Herein, we examined the joint associations of sedentary time and intensity-specific physical activity with all-cause and cardiovascular disease (CVD) mortality. METHODS: Prospective cohort study including 73,729 adults from the UK Biobank who wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days, being one a weekend day, between June 2013 and December 2015. We considered the median tertile values of sedentary time and physical activity in each intensity band to determine the amount of physical activity needed to attenuate the association between sedentary time and mortality. RESULTS: During a median of 6.9 years of follow-up (628,807 person-years), we documented 1521 deaths, including 388 from CVD. Physical activity of any intensity attenuated the detrimental association of sedentary time with mortality. Overall, at least a median of 6 min/day of vigorous physical activity, 30 min/day of MVPA, 64 min/day of moderate physical activity, or 163 min/day of light physical activity (mutually-adjusted for other intensities) attenuated the association between sedentary time and mortality. High sedentary time was associated with higher risk of CVD mortality only among participants with low MVPA (HR 1.96; 95% CI 1.23 to 3.14). CONCLUSIONS: Different amounts of each physical activity intensity may attenuate the association between high sedentary time and mortality.

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Worldwide, as well as in Mexico, the leading cause of death is cardiovascular disease (CVD). Hypertension is the main risk factor for CVD; about 50% of the adult population suffers from this condition. High sodium (Na) intake combined with low potassium (K) intake can trigger cardiovascular disorders such as high blood pressure (BP). The aim of this study was to estimate the mean excretion of Na and K in Mexican adults using a spot urine sample, and its association with cardiovascular disorders. Information on 2,778 adults, 20-59 years of age, who participated in ENSANUT-2016 was analyzed. Na and K were estimated using Tanaka formulae. Biomarkers such as glucose, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol, and anthropometry were measured. Mean Na was 3,354 mg/day (95%CI: 3,278, 3,429), 1,440 mg/day of K (95%CI: 1,412, 1,469), and the Na-K ratio was 2.4. The excretion of Na was greater in adults with high BP (3,542 mg/day) compared to those with normal BP (3,296 mg/day). In adults with hypertension, excretion of K was 10% greater (1,534 mg/day) than in adults with normal BP (1,357 mg/day). In adults with moderate reduction of renal function, Na excretion was 22% less (2,772 mg/day) than in adults with normal kidney function (3,382 mg/day). The results of this study show that the cardiovascular health of Mexican adults is at risk, as they showed high Na excretion and low K excretion.

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Background: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally. Methods: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised for marketing and/or included in EMLs and clinical guidelines. In each country, we collected retail and price data for polypills from at least one public-sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable if the lowest-paid worker spent more than a day's wage to purchase a monthly supply. Results: Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. In the four countries, no surveyed public pharmacies stocked polypills. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Private sector availability was 100% in Argentina and Spain. Most combinations (n = 5) identified were in India. Combinations found in India and Spain were affordable in the local context. A lowest-paid government worker would spend between 0.2 (India) and 2.8 (Mauritius) days' wages to pay the price for one month's supply of the polypills. Polypills were likely to be affordable if they were manufactured in the same country. Conclusion: Low availability and affordability of polypills in the public sector suggest that implementation remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

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Background: Hematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoter to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream-gene regulation in megakaryocytes and platelets are unknown. Objectives: To understand the regulation of RUNX1 and its target genes by RUNX1 isoforms. Methods: We performed studies on RUNX1 isoforms in megakaryocytic HEL cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD). Results: In chromatin immunoprecipitation and luciferase promoter assays, RUNX1 isoforms B and C bound and regulated P1 and P2 promoters. In HeLa cells RUNX1B decreased and RUNX1C increased P1 and P2 activities, respectively. In HEL cells, RUNX1B overexpression decreased RUNX1C and RUNX1A expression; RUNX1C increased RUNX1B and RUNX1A. RUNX1B and RUNX1C regulated target genes (MYL9, F13A1, PCTP, PDE5A and others) differentially in HEL cells. In platelets RUNX1B transcripts (by RNAseq) correlated negatively with RUNX1C and RUNX1A; RUNX1C correlated positively with RUNX1A. RUNX1B correlated positively with F13A1, PCTP, PDE5A, RAB1B, and others, and negatively with MYL9. In our previous studies, RUNX1C transcripts in whole blood were protective against acute events in CVD patients. We found that higher expression of RUNX1 targets F13A1 and RAB31 associated with acute events. Conclusions: RUNX1 isoforms B and C autoregulate RUNX1 and regulate downstream genes in a differential manner and this associates with acute events in CVD.

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AIMS: To external validate the SCORE2, AHA/ACC Pooled Cohort Equation (PCE), Framingham Risk Score (FRS), Non-Laboratory INTERHEART Risk Score (NL-IHRS), Globorisk-LAC, and WHO prediction models and compare their discrimination and calibration capacity. METHODS: Validation in individuals aged 40-69 years with at least 10 years follow-up and without baseline use of statins or cardiovascular diseases from the Prospective Urban Rural Epidemiology prospective cohort study (PURE)-Colombia. For discrimination, the C-statistic, and Receiver Operating Characteristic curves with the integrated area under the curve (AUCi) were used and compared. For calibration, the smoothed time-to-event method was used, choosing a recalibration factor based on the integrated calibration index (ICI). In the NL-IHRS, linear regressions were used. RESULTS: In 3,802 participants (59.1% women), baseline risk ranged from 4.8% (SCORE2 women) to 55.7% (NL-IHRS). After a mean follow-up of 13.2 years, 234 events were reported (4.8 cases per 1000 person-years). The C-statistic ranged between 0.637 (0.601-0.672) in NL-IHRS and 0.767 (0.657-0.877) in AHA/ACC PCE. Discrimination was similar between AUCi. In women, higher overprediction was observed in the Globorisk-LAC (61%) and WHO (59%). In men, higher overprediction was observed in FRS (72%) and AHA/ACC PCE (71%). Overestimations were corrected after multiplying by a factor derived from the ICI. CONCLUSIONS: Six prediction models had a similar discrimination capacity, supporting their use after multiplying by a correction factor. If blood tests are unavailable, NL-IHRS is a reasonable option. Our results suggest that these models could be used in other countries of Latin America after correcting the overestimations with a multiplying factor.

Detecting people at high risk of cardiovascular disease and implementing preventive interventions in this population is a key strategy in primary prevention. Recently, new risk calculation tools have been developed, but before their application and routine use in populations different from those where it was developed, it's necessary to validate them. The recommendations for predicting cardiovascular risk in Colombia's guidelines are based on studies with noteworthy limitations. This study involving 3,802 healthy individuals in Colombia supports the recommendation of using these prediction models. The estimation result should be multiplied by a correction factor, because most of the prediction models overestimate cardiovascular risk. For example, the correction factors suggested in women for AHA/ACC PCE and SCORE2 are 0.54 and 0.75, respectively. In men, the correction factors suggested in AHA/ACC PCE and SCORE2 are 0.28 and 0.61, respectively. Therefore, the present study with a contemporary population provides additional evidence to update these recommendations in Colombia and perhaps in Latin America.

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BACKGROUND: The COVID-19 pandemic has highlighted a correlation between cardiac complications and elevated cardiac biomarkers, which are linked to poorer clinical outcomes. OBJECTIVE: This study aims to determine the clinical impact of cardiac biomarkers in COVID-19 patients in Latin America. SUBJECTS AND METHODS: The CARDIO COVID 19-20 Registry is a multicenter observational study across 44 hospitals in Latin America and the Caribbean. It included hospitalized COVID-19 patients (n = 476) who underwent troponin, natriuretic peptide, and D-dimer tests. Patients were grouped based on the number of positive biomarkers. RESULTS: Among the 476 patients tested, 139 had one positive biomarker (Group C), 190 had two (Group B), 118 had three (Group A), and 29 had none (Group D). A directly proportional relationship was observed between the number of positive biomarkers and the incidence of decompensated heart failure. Similarly, there was a proportional relationship between the number of positive biomarkers and increased mortality. In Group B, patients with elevated troponin and natriuretic peptide and those with elevated troponin and D-dimer had 1.4 and 1.5 times higher mortality, respectively, than those with elevated natriuretic peptide and D-dimer. CONCLUSIONS: In Latin American COVID-19 patients, a higher number of positive cardiac biomarkers is associated with increased cardiovascular complications and mortality. These findings suggest that cardiac biomarkers should be utilized to guide acute-phase treatment strategies.

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Background: The objective of this research is to evaluate the efficacy and safety of drugs in the residual risk in any of its three components: lipid, inflammatory and thrombotic risk. Methods: A systematic review was conducted of randomized clinical trials that included as a primary outcome, at least one of the conditions related to atherosclerotic cardiovascular disease. The databases used were PUBMED/MEDLINE, Scopus and ClinicalTrials.gov. The risk of bias of the studies was assessed using the Risk of Bias 2 tool. Results: and discussion: 18 studies were included in the analysis. Half of the studies had low risk of bias or some concerns. Several drugs were effective in reducing the primary outcome: ethyl eicosapentaenoeic acid (17.2 % E-EPA versus 22 % placebo HR: 0.75; 95 % CI 0.68-0.83; p < 0.001), colchicine in stable coronary artery disease (6.8 % vs placebo 9.6 %, HR 0.59, 95 % CI 0.57-0.83; p < 0.001), Canakinumab (150 mg vs placebo ARR 15 %, HR 0.85, 95 % CI 0.74-0.98; p = 0.021) and Rivaroxaban with Aspirin in stable atherosclerotic disease (4.1 % versus aspirin 5.4 %, HR 0.76, 95 % CI 0.66-0.86, P < 0.001). Serious adverse events did not differ between study groups, except for a higher rate of bleeding with the use of combination antithrombotic therapy. Conclusion: The residual risk can be reduced through the use of different drugs that act by modifying atherogenic lipid levels, modulating inflammatory pathways and the risk of thrombosis, with an acceptable safety profile in most studies.

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The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 µg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production.

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