Introducción: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. Objetivo: Identificar los factores ...de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. Métodos: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. Resultados: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. Conclusiones: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.
Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF.
To identify cardiometabolic risk factors (CMRF) and ...antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender.
CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender.
Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women.
Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.
Documenting the patterns of oral anticoagulation therapy (OAT) is essential to prevent thromboembolic complications of nonvalvular atrial fibrillation (NVAF).
To report the patterns of OAT according ...to age and thromboembolic risk in patients included in CARMEN-AF, a nationwide registry of NVAF in Mexico, an upper middle-income country.
There were 1,423 consecutive patients ≥18 years old and with at least one thromboembolic risk factor enrolled in the CARMEN-AF Registry at their regular clinical visit during a three-year period. They were analyzed according to 1) age, 2) AF type, and 3) CHA
DS
-VASc score.
Overall, 16.4% of patients did not receive antithrombotic treatment, 19.4% received antiplatelet drugs (APD), 29.2% vitamin K antagonists (VKA), and 34.6% direct oral anticoagulants (DOAC). With increasing age, the proportion of subjects treated with VKA decreased significantly from 36.2% in subjects <65 years to 22.5% in those ≥75 years old (
<0.0001). Concomitantly, an increase in both APD and no antithrombotic treatment was observed with increasing age. DOAC were prescribed equally among all age groups (34.2% in <65, 36.0% in 65-74, and 33.9% in ≥75). According to the type of AF, VKA use was more common in patients with permanent AF (32.7%). A lower use of DOAC was observed in high thromboembolic risk subjects (33.6% in CHA
DS
-VASc ≥2) compared with the moderate risk group (41% in CHA
DS
-VASc = 1).
VKA use for NVAF in Mexico decreased in relation to increasing age. The proportion of DOAC therapy was the same in all age groups. Nevertheless, elderly patients with high thromboembolic risk received a suboptimal thromboprophylaxis. These data could help to improve gaps in the implementation of global guidelines.
http://www.clinicaltrials.gov. Unique identifier: NCT02334852.
CARMEN-AF is a nationwide multi-centric registry seeking to bridge the data gap on anticoagulation therapy for NVAF in Mexico.Elderly patients are more prone to receive suboptimal OAT for NVAF.DOAC were less frequently used in high thromboembolic risk patients (CHA
DS
-VASc ≥2).
The study of Hutchinson–Gilford progeria syndrome (HGPS) has provided important clues to decipher mechanisms underlying aging. Progerin, a mutant lamin A, disrupts nuclear envelope ...structure/function, with further impairment of multiple processes that culminate in senescence. Here, we demonstrate that the nuclear protein export pathway is exacerbated in HGPS, due to progerin‐driven overexpression of CRM1, thereby disturbing nucleocytoplasmic partitioning of CRM1‐target proteins. Enhanced nuclear export is central in HGPS, since pharmacological inhibition of CRM1 alleviates all aging hallmarks analyzed, including senescent cellular morphology, lamin B1 downregulation, loss of heterochromatin, nuclear morphology defects, and expanded nucleoli. Exogenous overexpression of CRM1 on the other hand recapitulates the HGPS cellular phenotype in normal fibroblasts. CRM1 levels/activity increases with age in fibroblasts from healthy donors, indicating that altered nuclear export is a common hallmark of pathological and physiological aging. Collectively, our findings provide novel insights into HGPS pathophysiology, identifying CRM1 as potential therapeutic target in HGPS.
HGPS cells show enhanced nuclear protein export activity due to CRM1 overexpression. Ectopic overexpression of CRM1 recreates HGPS‐associated aging features in normal cells. Pharmacological modulation of CRM1 activity alleviates the HGPS phenotype.
The cardiovascular disease pandemic has promoted the cardiovascular polypill as one of the most scalable public health strategies to improve cardiovascular risk by increasing accessibility and ...adherence to treatments. Data from randomized clinical trials has shown that the polypill strategy significantly improves adherence as well as risk factor control (cholesterol and blood pressure), however, to date, no information from phase IV registries has been available.
We conducted a multicentre, observational and prospective registry of a polypill-based treatment strategy. A total of 1193 patients in Mexico were included. Patient demographics, clinical history, blood pressure, analysis of blood lipids and the Framingham risk score were measured at baseline and after 12 months of treatment with the CNIC-Ferrer polypill.
At one year with the polypill, systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels changed from mean 146.9 mmHg to 128 mmHg (p <0.001), and from 89.1 mmHg to 80.4 mmHg (p <0.001) respectively. LDLc levels were significantly reduced 132.5–107.6 mg/dL (p <0.001). The 10 year Framingham cardiovascular disease risk was also reduced in the high-risk group (33.7 + 22.0 vs. 21.2 + 14.8; p <0.001) and in the intermediate risk group (23.7 + 14.8 vs. 12.7 + 11.4; p <0.001).
To our knowledge, the results of the current study constitute the first real life data on the impact of a polypill therapy on cardiovascular risk factor control. The results show major improvements on the primary outcome, above and beyond those presented previously in the setting of randomized clinical trials.
β-dystroglycan (β-DG) is a key component of multiprotein complexes in the plasma membrane and nuclear envelope. In addition, β-DG undergoes two successive proteolytic cleavages that result in the ...liberation of its intracellular domain (ICD) into the cytosol and nucleus. However, stimuli-inducing ICD cleavage and the physiological relevance of this proteolytic fragment are largely unknown. In this study we show for the first time that β-DG ICD is targeted to the nucleolus where it interacts with the nuclear proteins B23 and UBF (central factor of Pol I-mediated rRNA gene transcription) and binds to rDNA promoter regions. Interestingly DG silencing results in reduced B23 and UBF levels and aberrant nucleolar morphology. Furthermore, β-DG ICD cleavage is induced by different nucleolar stressors, including oxidative stress, acidosis, and UV irradiation, which implies its participation in the response to nucleolar stress. Consistent with this idea, overexpression of β-DG elicited mislocalization and decreased levels of UBF and suppression of rRNA expression, which in turn provoked altered ribosome profiling and decreased cell growth. Collectively our data reveal that β-DG ICD acts as negative regulator of rDNA transcription by impeding the transcriptional activity of UBF, as a part of the protective mechanism activated in response to nucleolar stress.
We describe the clinical characteristics and outcomes of adults hospitalized with pneumonia during the pandemic (H1N1) 2009 outbreak. Patients admitted to a general hospital in San Luis Potosí, ...Mexico, from April 10 through May 11, 2009, suspected to have influenza virus-associated pneumonia were evaluated. We identified 50 patients with suspected influenza pneumonia; the presence of influenza virus was confirmed in 18: 11 with pandemic (H1N1) 2009 virus, 5 with unsubtypeable influenza A virus, 1 with seasonal influenza A virus (H3N2), and 1 in whom assay results for seasonal and pandemic (H1N1) 2009 viruses were positive. Eighteen patients were treated in the intensive care unit, and 10 died. During the pandemic (H1N1) 2009 outbreak, severe pneumonia developed in young adults who had no identifiable risk factors; early diagnosis and treatment of influenza virus infections may have a determinant role in outcome.
Chronic kidney disease is a serious health problem in El Salvador. Since the 1990s, there has been an increase in cases unassociated with traditional risk factors. It is the second leading cause of ...death in men aged >18 years. In 2009, it was the first cause of in-hospital death for men and the fifth for women. The disease has not been thoroughly studied.
Characterize clinical manifestations (including extrarenal) and pathophysiology of chronic kidney disease of nontraditional causes in Salvadoran farming communities.
A descriptive clinical study was carried out in 46 participants (36 men, 10 women), identified through chronic kidney disease population screening of 5018 persons. Inclusion criteria were age 18-59 years; chronic kidney disease at stages 2, 3a and 3b, or at 3a and 3b with diabetes or hypertension and without proteinuria; normal fundoscopic exam; no structural abnormalities on renal ultrasound; and HIV-negative. Examinations included social determinants; psychological assessment; clinical exam of organs and systems; hematological and biochemical parameters in blood and urine; urine sediment analysis; markers of renal damage; glomerular and tubular function; and liver, pancreas and lung functions. Renal, prostate and gynecological ultrasound; and Doppler echocardiography and peripheral vascular and renal Doppler ultrasound were performed.
Patient distribution by chronic kidney disease stages: 2 (32.6%), 3a (23.9%), 3b (43.5%). Poverty was the leading social determinant observed. Risk factor prevalence: agrochemical exposure (95.7%), agricultural work (78.3%), male sex (78.3%), profuse sweating during work (76.3%), malaria (43.5%), NSAID use (41.3%), hypertension (36.9%), diabetes (4.3%). General symptoms: arthralgia (54.3%), asthenia (52.2%), cramps (45.7%), fainting (30.4). Renal symptoms: nycturia (65.2%), dysuria (39.1%), foamy urine (63%). Markers of renal damage: macroalbuminuria (80.4%), ß2 microglobulin (78.2%), NGAL (26.1%). Renal function: hypermagnesuria (100%), hyperphosphaturia (50%), hypernatriuria (45.7%), hyperkaluria (23.9%), hypercalciuria (17.4%), electrolyte polyuria (43.5%), metabolic alkalosis (45.7%), hyponatremia (47.8%), hypocalcemia (39.1%), hypokalemia (30.4%), hypomagnesemia (19.6%). Imaging: Ultrasound showed fatty liver (93.5%) and vascular Doppler showed tibial artery damage (66.7%). Neurological symptoms: abnormal tendon reflexes (45.6%), Babinski sign and myoclonus (6.5%), sensorineural hearing loss (56.5%).
This chronic kidney disease studied behaves clinically like chronic tubulointerstitial nephropathy, but with systemic manifestations not attributable to kidney disease. While male agricultural workers predominated, women and adolescents were also affected. Findings support a hypothesis of multifactorial etiology with a key role played by nephrotoxic environmental agents.
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