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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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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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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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Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project.
Gutiérrez-Carrasquilla, L, Sánchez, E, Hernández, M, Polanco, D, Salas-Salvadó, J, Betriu, À, Gaeta, AM, Carmona, P, Purroy, F, Pamplona, R, et al
Nutrients. 2019;11(2)
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The Mediterranean diet is characterised by an abundant consumption of extra-virgin olive oil, fruits, vegetables, nuts, and legumes, a moderate consumption of fish and seafood, poultry, fermented dairy products, and red wine with meals, and low intakes of sweetened beverages, red meat and ready meals. The aim of the study was to evaluate the association between adherence to a Mediterranean diet and physical activity on pulmonary function in a large middle-aged population at low-to-moderate cardiovascular risk. The study is an ongoing study that between 2015 and 2017 enrolled a total of 3020 subjects – women aged between 50 to 70 years and men aged between 45 to 65 years – with the presence of at least one cardiovascular risk factor. Results indicate that a low adherence to the Mediterranean diet was linked with impaired breathing patterns and higher prevalence of abnormal lung function when compared to participants with a higher adherence to this dietary pattern. Additionally, vigorous physical activity was accompanied by better results in lung function than that observed in inactive subjects. The study provides initial clinical evidence about the independent and deleterious effect of both low adherence to the Mediterranean diet and low physical activity practice on lung function in participants without known pulmonary disease.
Abstract
A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87⁻109) vs. 94 (82⁻105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89⁻112) vs. 93 (80⁻107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88⁻107) vs. 94 (83⁻105) % of predicted, p = 0.027) and FEV1 (100 (89⁻110) vs. 95 (84⁻108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.
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Lung function measurements in the prediabetes stage: data from the ILERVAS Project.
Sánchez, E, Gutiérrez-Carrasquilla, L, Barbé, F, Betriu, À, López-Cano, C, Gaeta, AM, Purroy, F, Pamplona, R, Ortega, M, Fernández, E, et al
Acta diabetologica. 2019;(9):1005-1012
Abstract
AIMS: Patients with type 2 diabetes have been considered a susceptible group for pulmonary dysfunction. Our aim was to assess pulmonary function on the prediabetes stage. METHODS Pulmonary function was assessed in 4,459 non-diabetic subjects, aged between 45 and 70 years, without cardiovascular disease or chronic pulmonary obstructive disease from the ongoing study ILERVAS. A "restrictive spirometric pattern", an "abnormal FEV1" and an "obstructive ventilatory defect" were assessed. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association criteria. RESULTS Population was composed of 52.1% women, aged 57 [53;63] years, a BMI of 28.6 [25.8;31.8] kg/m2, and with a prevalence of prediabetes of 29.9% (n = 1392). Subjects with prediabetes had lower forced vital capacity (FVC: 93 [82;105] vs. 96 [84;106], p < 0.001) and lower forced expired volume in the first second (FEV1: 94 [82;107] vs. 96 [84;108], p = 0.011), as well as a higher percentage of the restrictive spirometric pattern (16.5% vs. 13.6%, p = 0.015) and FEV1 < 80% (20.3% vs. 17.2%, p = 0.017) compared to non-prediabetes group. In the prediabetes group, HbA1c was negatively correlated with both pulmonary parameters (FVC: r = - 0.113, p < 0.001; FEV1: r = - 0.079, p = 0.003). The multivariable logistic regression model in the whole population showed that there was a significant and independent association between HbA1c with both restrictive spirometric pattern [OR = 1.42 (1.10-1.83), p = 0.008] and FEV1 < 80% [OR = 1.50 (1.19-1.90), p = 0.001]. CONCLUSIONS The deleterious effect of type 2 diabetes on pulmonary function appears to be initiated in prediabetes, and it is related to metabolic control. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03228459.
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Subcutaneous advanced glycation end-products and lung function according to glucose abnormalities: The ILERVAS Project.
Sánchez, E, Lecube, A, Betriu, À, Hernández, C, López-Cano, C, Gutiérrez-Carrasquilla, L, Kerkeni, M, Yeramian, A, Purroy, F, Pamplona, R, et al
Diabetes & metabolism. 2019;(6):595-598
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Subclinical atherosclerosis burden predicts cardiovascular events in individuals with diabetes and chronic kidney disease.
Palanca, A, Castelblanco, E, Betriu, À, Perpiñán, H, Soldevila, B, Valdivielso, JM, Bermúdez-Lopez, M, Puig-Jové, C, Puig-Domingo, M, Groop, PH, et al
Cardiovascular diabetology. 2019;(1):93
Abstract
BACKGROUND Individuals with diabetes have remarkably high rates of cardiovascular morbidity and mortality. However, the incremental cardiovascular risk in diabetes is heterogeneous and has often been related to renal involvement. The purpose of this study was to analyse the prognostic value of subclinical atherosclerosis in determining the incidence of first cardiovascular events (CVEs) in individuals with diabetes and chronic kidney disease (CKD) compared to CKD individuals without diabetes. METHODS We included data from individuals with CKD with and without diabetes, free from pre-existing cardiovascular disease, from the NEFRONA cohort. Participants underwent baseline carotid and femoral ultrasound and were followed up for 4 years. All CVEs during follow-up were registered. Bivariate analysis and Fine-Gray competing risk models were used to perform the statistical analysis. RESULTS During the mean follow-up time of 48 months, a total of 203 CVE was registered. 107 CVE occurred among participants without diabetes (19.58 per 1000 person-years) and 96 CVE occurred among participants with diabetes (44.44 per 1000 person-years). Following the competing risk analysis, the variables predicting CVEs in CKD individuals without diabetes were the number of territories with plaque at baseline (HR 1.862, 95% CI [1.432;2.240]), age (HR 1.026, 95% CI [1.003;1.049]) and serum concentrations of 25-OH vitamin D (HR 0.963, 95% CI [0.933;0.094]). The only variable predicting CVEs among CKD participants with diabetes was the number of territories with plaque at baseline (HR 1.782, 95% CI [1.393, 2.278]). For both models, concordance (C) index yielded was over 0.7. CONCLUSIONS The burden of subclinical atherosclerosis is the strongest predictor of future CVEs in diabetic individuals with CKD. Early detection of subclinical atherosclerotic burden by multiterritorial vascular ultrasound could improve CVE prediction in this population.
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Skin Autofluorescence Measurement in Subclinical Atheromatous Disease: Results from the ILERVAS Project.
Sánchez, E, Betriu, À, Yeramian, A, Fernández, E, Purroy, F, Sánchez-de-la-Torre, M, Pamplona, R, Miquel, E, Kerkeni, M, Hernández, C, et al
Journal of atherosclerosis and thrombosis. 2019;(10):879-889
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Abstract
AIM: Advanced glycation end-products (AGEs) have been involved in the atherogenic process in the high-risk population. The goal of this study was to demonstrate that AGEs are related to subclinical atheromatous disease in subjects with low to moderate vascular risk. METHODS A cross-sectional study in which 2,568 non-diabetic subjects of both sexes without cardiovascular disease were included. Subcutaneous content of AGEs was assessed by skin autofluorescence (SAF) and subclinical atheromatous disease was measured by assessing the atheromatous plaque burden in carotid and femoral regions using ultrasonography. In addition, serum pentosidine, carboxymethyl-lysine (CML) and AGE receptors (RAGE) were assessed in a nested case-control study with 41 subjects without plaque and 41 individuals subjects with generalized disease. RESULTS Patients with atheromatous plaque had a higher SAF than those with no plaque (1.9 [1.7 to 2.3] vs. 1.8 [1.6 to 2.1] arbitrary units (AU), p<0.001). The SAF correlated with the total number of affected regions (r= 0.171, p<0.001), increasing progressively from 1.8 [1.6 to 2.1] AU in those without atheromatous disease to 2.3 [1.9 to 2.7] AU in patients with ≥ 8 plaques (p<0.001). A correlation was also observed between SAF and the total plaque area (r=0.113, p<0.001). The area under the Receiver Operating Characteristic curve was 0.65 (0.61 to 0.68) for identifying male subjects with atheromatous disease. The multivariable logistic regression model showed a significant and independent association between SAF and the presence of atheromatous disease. However, no significant differences in serum pentosidine, CML, and RAGE were observed. CONCLUSIONS Increased subcutaneous content of AGEs is associated with augmented atheromatous plaque burden. Our results suggest that SAF may provide clinically relevant information to the current strategies for the evaluation of cardiovascular risk, especially among the male population.
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The influence of sleep apnea syndrome and intermittent hypoxia in carotid adventitial vasa vasorum.
López-Cano, C, Rius, F, Sánchez, E, Gaeta, AM, Betriu, À, Fernández, E, Yeramian, A, Hernández, M, Bueno, M, Gutiérrez-Carrasquilla, L, et al
PloS one. 2019;(2):e0211742
Abstract
Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous disease.
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Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project.
Sánchez, E, Betriu, À, López-Cano, C, Hernández, M, Fernández, E, Purroy, F, Bermúdez-López, M, Farràs-Sallés, C, Barril, S, Pamplona, R, et al
Cardiovascular diabetology. 2019;(1):154
Abstract
BACKGROUND Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage. METHODS Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines. RESULTS Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects. CONCLUSIONS The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner. Trial registration NCT03228459 (clinicaltrials.gov).