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1.
Weak Association between Skin Autofluorescence Levels and Prediabetes with an ILERVAS Cross-Sectional Study.
Sánchez, E, Kerkeni, M, Hernández, M, Gavaldà, R, Rius, F, Sauret, A, Torres, G, Bermúdez-López, M, Fernández, E, Castro-Boqué, E, et al
Nutrients. 2022;(5)
Abstract
A large body of evidence demonstrates a relationship between hyperglycemia and increased concentrations of advanced glycation end-products (AGEs). However, there is little information about subcutaneous AGE accumulation in subjects with prediabetes, and whether or not this measurement could assist in the diagnosis of prediabetes is unclear. A cross-sectional study was conducted in 4181 middle-aged subjects without diabetes. Prediabetes (n = 1444) was defined as a glycosylated hemoglobin (HbA1c) level between 39 and 47 mmol/mol (5.7 to 6.4%), and skin autofluorescence (SAF) measurement was performed to assess AGEs. A multivariable logistic regression model and receiver operating characteristic curve were used. The cohort consisted of 50.1% women with an age of 57 [52;62] years, a BMI of 28.3 [25.4;31.6] kg/m2, and a prevalence of prediabetes of 34.5%. Participants with prediabetes showed higher SAF than control participants (2.0 [1.7;2.2] vs. 1.9 [1.7;2.2], p < 0.001). However, HbA1c was not significantly correlated with SAF levels (r = 0.026, p = 0.090). In addition, the SAF level was not independently associated with prediabetes (OR = 1.12 (0.96 to 1.30)). Finally, there was no good cutoff point for SAF to identify patients with prediabetes (AUC = 0.52 (0.50 to 0.54), sensitivity = 0.61, and 1-specificity = 0.56). Given all of this evidence, we can conclude that although there is an increase in SAF levels in participants with prediabetes, the applicability and clinical relevance of the results is low in this population.
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2.
Proprotein convertase subtilisin/kexin type 9 inhibitors in secondary prevention of vascular events in patients with stroke: Consensus document and practice guidance.
Gil-Núñez, A, Masjuan, J, Montaner, J, Castellanos, M, Segura, T, Cardona, P, Tembl, JI, Purroy, F, Arenillas, J, Palacio, E
Neurologia. 2022;(2):136-150
Abstract
INTRODUCTION Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. METHODS A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. CONCLUSIONS PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels < 20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.
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3.
Prediabetes Is Associated with Increased Prevalence of Sleep-Disordered Breathing.
Sánchez, E, Sapiña-Beltrán, E, Gavaldà, R, Barbé, F, Torres, G, Sauret, A, Dalmases, M, López-Cano, C, Gutiérrez-Carrasquilla, L, Bermúdez-López, M, et al
Journal of clinical medicine. 2022;(5)
Abstract
Type 2 diabetes leads to severe nocturnal hypoxemia, with an increase in apnea events and daytime sleepiness. Hence, we assessed sleep breathing parameters in the prediabetes stage. A cross-sectional study conducted on 966 middle-aged subjects without known pulmonary disease (311 patients with prediabetes and 655 controls with normal glucose metabolism) was conducted. Prediabetes was defined by glycated hemoglobin (HbA1c), and a nonattended overnight home sleep study was performed. Participants with prediabetes (n = 311) displayed a higher apnea−hypopnea index (AHI: 12.7 (6.1;24.3) vs. 9.5 (4.2;19.6) events/h, p < 0.001) and hypopnea index (HI: 8.4 (4.0;14.9) vs. 6.0 (2.7;12.6) events/h, p < 0.001) than controls, without differences in the apnea index. Altogether, the prevalence of obstructive sleep apnea was higher in subjects with prediabetes than in controls (78.1 vs. 69.9%, p = 0.007). Additionally, subjects with prediabetes presented impaired measurements of the median and minimum nocturnal oxygen saturation, the percentage of time spent with oxygen saturations below 90%, and the 4% oxygen desaturation index in comparison with individuals without prediabetes (p < 0.001 for all). After adjusting for age, sex, and the presence of obesity, HbA1c correlated with the HI in the entire population (r = 0.141, p < 0.001), and the presence of prediabetes was independently associated with the AHI (B = 2.20 (0.10 to 4.31), p = 0.040) as well as the HI (B = 1.87 (0.61 to 3.14), p = 0.004) in the multiple linear regression model. We conclude that prediabetes is an independent risk factor for an increased AHI after adjusting for age, sex, and obesity. The enhanced AHI is mainly associated with increments in the hypopnea events.
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4.
Prevalence and Predictors of Cerebral Microangiopathy Determined by Pulsatility Index in an Asymptomatic Population From the ILERVAS Project.
Purroy, F, Sánchez, E, Lecube, A, Arqué, G, Vicente-Pascual, M, Mauri-Capdevila, G, Torreguitart, N, Hernández, M, Barbé, F, Fernández, E, et al
Frontiers in neurology. 2021;:785640
Abstract
Background: Little is known about the prevalence of cerebral microangiopathy (CM), which is related to cognitive impairment, in an asymptomatic population. Pulsatility index (PI) is an easily measurable parameter of cerebral vascular resistance in transcranial duplex of the middle cerebral artery (MCA) study. We aimed to determine the prevalence of CM measured by PI of MCA in low to moderate vascular risk subjects. Methods: We included 3,721 subjects between 45 and 70 years without previous history of vascular disease or diabetes mellitus and with at least one other vascular risk factor from the cross-sectional study ILERVAS (Lleida, Spain). Patients underwent transcranial duplex to determine MCA-PI. Possible CM was defined by MCA-PI >1.1. Carotid and femoral arteries ultrasound registration was done to determine the presence, the number, and the area of atheromatous plaques. Body mass index (BMI), pulse pressure (PP) and laboratory data were also recorded. Results: 439 (11.8%) subjects were excluded due to the low quality of transcranial duplex images. Median age was 57 [IQR 52, 62] years. Possible CM was found in 424 (12.9%) subjects. CM patients had higher prevalence of plaques than non-CM (77.4 vs. 66.4%, p < 0.001). PI showed a positive linear correlation with the number of territories with plaques (r = 0.130, p < 0.001), and the total plaque area (r = 0.082, p < 0.001). The predictors of possible CM were the age, male gender, and PP. Conclusions: In low-to-moderate vascular risk asymptomatic population, the proportion of abnormal brain microvascular bed determined by MCA-PI is not negligible. The planned 10-year follow-up will describe the clinical relevance of these findings.
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5.
Subclinical atheromatosis localization and burden in a low-to-moderate cardiovascular risk population: the ILERVAS study.
Bermúdez-López, M, Martínez-Alonso, M, Castro-Boqué, E, Betriu, À, Cambray, S, Farràs, C, Barbé, F, Pamplona, R, Lecube, A, Mauricio, D, et al
Revista espanola de cardiologia (English ed.). 2021;(12):1042-1053
Abstract
INTRODUCTION AND OBJECTIVES There is a discrepancy between risk assessment based on cardiovascular risk factors (CVRF) and atheromatosis burden. The objective was to identify the prevalence of subclinical diseases with common risk factors, such as atheromatosis, occult kidney disease, prediabetes, and diabetes in a middle-aged population with low-to-moderate cardiovascular risk; to assess the vascular distribution, and severity of subclinical atheromatosis. METHODS Randomized, interventional, longitudinal clinical trial. The intervention consisted of vascular ultrasound examination in the carotid and femoral arteries assessing 12 territories, combined with clinical, anthropometric, lifestyle, and biochemical parameters. Inclusion criteria consisted of women (aged 50-70 years) and men (aged 45-65 years) with at least 1 CVRF. Exclusion criteria consisted of a clinical history of diabetes, chronic kidney disease, or a prior CV event. Here, baseline characteristics of the ILERVAS cohort are shown. RESULTS A total of 8330 middle-aged asymptomatic participants, 50.7% women, were enrolled. The presence of 1-2 CVRF was found in 74.8% and adherence to the Mediterranean diet was low in 52.8%. Several previously unknown chronic diseases were diagnosed, such as dyslipidemia (21.1%), hypertension (15.3%), kidney disease (15.4%), obesity (10.6%), and diabetes (2.3%). Subclinical atheromatosis was found in 71.4% of participants, localized in common femoral (54.5%), carotid bifurcation (41.1%) and internal carotid (22%). Intermediate atheromatosis (2-3 territories with atheroma plaque) was found in 32.6%, and generalized atheromatosis (>3 territories) in 19.7. Total plaque area was higher in men (0.97 cm2 vs 0.58 cm2, P<.001). Total plaque area was also higher in the femoral artery, and increased with the number of CVRF. CONCLUSIONS Subclinical atheromatosis was highly prevalent in a middle-aged population with low-to moderate cardiovascular risk, with 1 in 5 participants having generalized atheromatosis. ClinicalTrials.gov Identifier: NCT03228459.
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6.
Clinical Usefulness of Anthropometric Indices to Predict the Presence of Prediabetes. Data from the ILERVAS Cohort.
Sánchez, M, Sánchez, E, Bermúdez-López, M, Torres, G, Farràs-Sallés, C, Pamplona, R, Castro-Boqué, E, Valdivielso, JM, Purroy, F, Martínez-Alonso, M, et al
Nutrients. 2021;(3)
Abstract
Prediabetes is closely related to excess body weight and adipose distribution. For this reason, we aimed to assess and compare the diagnostic usefulness of ten anthropometric adiposity indices to predict prediabetes. Cross-sectional study with 8188 overweight subjects free of type 2 diabetes from the ILERVAS project (NCT03228459). Prediabetes was diagnosed by levels of glycated hemoglobin (HbA1c). Total body adiposity indices [BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) and Deurenberg's formula] and abdominal adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body shape index, and body roundness index) were calculated. The area under the receiver-operating characteristic (ROC) curve, the best cutoff and the prevalence of prediabetes around this value were calculated for every anthropometric index. All anthropometric indices other than the A body adiposity were higher in men and women with prediabetes compared with controls (p < 0.001 for all). In addition, a slightly positive correlation was found between indices and HbA1c in both sexes (r ≤ 0.182 and p ≤ 0.026 for all). None of the measures achieved acceptable levels of discrimination in ROC analysis (area under the ROC ≤ 0.63 for all). Assessing BMI, the prevalence of prediabetes among men increased from 20.4% to 36.2% around the cutoff of 28.2 kg/m2, with similar data among women (from 29.3 to 44.8% with a cutoff of 28.6 kg/m2). No lonely obesity index appears to be the perfect biomarker to use in clinical practice to detect individuals with prediabetes.
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7.
Mediterranean diet, physical activity and subcutaneous advanced glycation end-products' accumulation: a cross-sectional analysis in the ILERVAS project.
Sánchez, E, Betriu, À, Salas-Salvadó, J, Pamplona, R, Barbé, F, Purroy, F, Farràs, C, Fernández, E, López-Cano, C, Mizab, C, et al
European journal of nutrition. 2020;(3):1233-1242
Abstract
PURPOSE Adherence to Mediterranean diet (MedDiet) and physical activity have been associated to lower cardiovascular risk and mortality. Our purpose was to test the modification of advanced glycation end-products (AGEs) as one of the underlying mechanisms explaining this relationship. METHODS Cross-sectional study assessing the adherence to MedDiet (14-item Mediterranean Diet Adherence Screener) and physical activity (International Physical Activity Questionnaire short form) in 2646 middle-aged subjects without known cardiovascular disease and type 2 diabetes from the ILERVAS study. Skin autofluorescence (SAF), a non-invasive assessment of subcutaneous AGEs, was measured. Multivariable logistic regression models were done to study interactions and independent associations with a likelihood ratio test. RESULTS Participants with a high adherence to MedDiet had lower SAF than those with low adherence (1.8 [IR 1.6; 2.1] vs. 2.0 [IR 1.7; 2.3] arbitrary units, p < 0.001), without differences according to categories of physical activity. There was an independent association between high adherence to MedDiet and the SAF values [OR 0.59 (0.37-0.94), p = 0.026]. When adherence to MedDiet was substituted by its individual food components, high intake of vegetables, fruits and nuts, and low intake of sugar-sweetened soft beverages were independently associated with a decreased SAF (p ≤ 0.045). No interaction between MedDiet and physical activity on SAF values was observed except for nuts consumption (p = 0.047). CONCLUSIONS Adherence to the MedDiet, but not physical activity, was negatively associated to SAF measurements. This association can be explained by some typical food components of the MedDiet. The present study offers a better understanding of the plausible biological conditions underlying the prevention of cardiovascular disease with MedDiet. ClinTrials.gov identifier: NCT03228459.
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8.
Are Obesity Indices Useful for Detecting Subclinical Atheromatosis in a Middle-Aged Population?
Sánchez, E, Sánchez, M, Betriu, À, Rius, F, Torres, G, Purroy, F, Pamplona, R, Ortega, M, López-Cano, C, Hernández, M, et al
Obesity facts. 2020;(1):29-39
Abstract
OBJECTIVE There is a close relationship between excess adiposity and cardiovascular disease. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. Here, our objective was to assess the usefulness of these anthropometric indices to detect subclinical atheromatous disease. METHODS A cross-sectional study with 6,809 middle-aged subjects (mean age, 57 [53-63] years) with low to moderate cardiovascular risk from the ILERVAS project. Measures of total body fat (BMI, Clínica Universidad de Navarra - Body Adiposity Estimator [CUN-BAE], and Deurenberg's formula) and central adiposity (waist and neck circumferences, conicity index, waist-to-height ratio, Bonora's equation, the A body adiposity index, and body roundness index) were performed in all participants. Bilateral carotid and femoral ultrasound vascular studies allowed the identification of subjects with plaque. -Results: All measured indices were significantly higher in males with subclinical carotid or femoral plaques (p ≤ 0.021 for all). Also, a positive and significant correlation between all indices and the number of affected territories was found (p ≤ 0.013 for all). From the ROC analysis, all measurements identified patients with asymptomatic atheromatosis but none of them helped make clinical decisions. Regarding females, the results were less conclusive. CONCLUSION Obesity indices are related to subclinical atheromatosis, especially in men, in a large cohort of middle-aged subjects. However, the indices could not detect the presence of arterial plaque, so, when used in isolation, are unlikely to be decisive.
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9.
[Hypokalemic periodic paralysis: a systematic review of published case reports].
Latorre, R, Purroy, F
Revista de neurologia. 2020;(9):317-325
Abstract
INTRODUCTION Hypokalemic periodic paralysis is a neuromuscular disease characterized by a combination of flaccid paralysis episodes (or muscular weakness) that are related to low levels of potassium in blood. As a consequence of its low prevalence, there are still clinical and management aspects to characterize. PATIENTS AND METHODS A systematic review of the clinical cases published in the last decade has been developed by analyzing demographic and genetic features, the episodes' characteristics, the received treatments, the response to them and also, the differences and evolution of patients depending on the most prevalent genetic alterations: CACNA1S and SCN4A. RESULTS A total of 33 articles were included, allowing 40 individuals to be reviewed. The average age of onset of symptoms was 15.3 ± 9.7 years. The most frequent altered gene was CACNA1S in 20 (60.5%) cases. It was observed that subjects presenting an alteration of the gene responsible for the calcium channel, CACNA1S, presented lower serum potassium levels, own triggers and a higher proportion of subjects showing dyspnea during the crisis. Only 50% of the subjects respond to classical oral treatment with acetazolamide. Potassium-sparing diuretics and antiepileptics drugs emerge as an alternative. CONCLUSION Hypokalemic periodic paralysis has an heterogeneous clinical expression with phenotypic differences linked to different genetic mutations. The common preventive treatment response is suboptimal. Prospective studies are needed to discern the best therapeutic option based on genetic load.
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10.
REMOTE Ischemic Perconditioning Among Acute Ischemic Stroke Patients in Catalonia: REMOTE-CAT PROJECT.
Purroy, F, Arque, G, Mauri, G, García-Vázquez, C, Vicente-Pascual, M, Pereira, C, Vazquez-Justes, D, Torres-Querol, C, Vena, A, Abilleira, S, et al
Frontiers in neurology. 2020;:569696
Abstract
Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection. Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care. Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%. Methods and Design: We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device. Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days. Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03375762.