Clínica e Investigación en Arteriosclerosis (English Edition)最新文献

Objective

To assess thrombotic risk with PAI-1 levels in patients with COVID-19, to evaluate PAI-1 differences between hyperglycemic and/or Type 2 Diabetes Mellitus (T2DM) versus non-hyperglycemic patients, and to analyze the association of plasminogen activator inhibitor-1 (PAI-1) with hyperglycemia and T2DM.

Methods

A cross-sectional study carried out in 181 patients hospitalized for COVID-19. Two groups were formed: the patients with hyperglycemia at admission and/or previously diagnosed T2DM group and the non-hyperglycemic group. Fibrinolysis was assessed by measuring PAI-1 levels by ELISA.

Results

The mean age was 59.4 ± 16.1 years; 55.8% were male 54.1% of patients presented obesity, 38.1% had pre-existing T2DM and 50.8% had admission hyperglycemia and/or pre-existing T2DM. The patients with admission hyperglycemia and/or preexisting T2DM had higher PAI-1 compared with non-hyperglycemic patients [197.5 (128.8–315.9) vs 158.1 (113.4–201.4) ng/mL; p = 0.031]. The glucose levels showed a positive correlation with PAI-1 levels (r = 0.284, p = 0.041). A multivariate logistic regression analysis showed association of PAI-1 level and hyperglycemia and pre-existing T2DM with severity of COVID-19.

Conclusion

Patients hospitalized for COVID-19 infection with preexisting T2DM or hyperglycemia detected during their hospitalization presented a greater increase in PAI-1 levels, which suggests that hyperglycemia contributes directly to the hypercoagulable state and probably a worse outcome from the patients.

Familial hypobetalipoproteinaemia is a disorder of lipid metabolism characterized by low levels of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B. ApoB-related familial hypolipoproteinemia is an autosomal condition with a codominance inheritance pattern. Non-classical congenital adrenal hyperplasia is an autosomal recessive disorder due to mutations in the CYP21A2, a gene encoding for the enzyme 21-hydroxylase, which results in an androgen excess production from adrenal source. We here present the case of a 25-year-old woman with NCAH showing decreased levels of total-cholesterol, low-density lipoprotein cholesterol and triglycerides. Her parent had digestive symptoms and severe hepatic steatosis with elevated liver enzymes, as well as decreased levels of total and low-density lipoprotein cholesterol. A genetic-molecular study of the proband identified a mutation in the APOB gene, which allowed a diagnosis of heterozygous ApoB-related hypolipoproteinaemia to be made.

Cardiovascular disease secondary to atherosclerosis is the main cause of morbidity and mortality in the world. Cardiovascular risk stratification has proven to be an insufficient approach to detect those subjects who are going to suffer a cardiovascular event, which is why for years other markers have been sought to help stratify each individual with greater precision. Two-dimensional vascular ultrasound is a excellent method for vascular risk assessment.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment. Finally, it presents aspects that are not usually referenced in the literature, such as the organisation of a vascular risk consultation.

Background

This study aimed to validate the IberScore cardiovascular risk model in a population attended in the primary care setting.

Methods

A cohort of patients with no history of cardiovascular disease visited in a primary care center during the years 2008 and/or 2009 and followed up until 2018 was selected.

Cardiovascular risk was calculated with the IberScore formula for all the subjects of the cohort and the model was calibrated, graphically represented by risk deciles the proportion of expected events and proportion of observed events at 10-year follow-up, stratified by sex. The area under the ROC curve was calculated to assess the discrimination of the model.

Results

A total of 10,085 patients visited during the years 2008 and/or 2009 were included in the study. Men showed a mean 10-year risk of suffering a fatal or non-fatal cardiovascular events according to IberScore of 17.07% (SD 20.13), with a mean estimated vascular age of more than 4 years higher than the biological age; while women had a mean 10-year risk of 7.91% (SD 9.03), with an estimated vascular age of more than 2 years above the biological age.

The area under the ROC curve showed a discrimination index of the model of 0.86 (95% CI 0.84–0.88) in men and 0.82 (95% CI 0.79–0.85) in women.

Conclusion

IberScore model discriminates well in the population attended in primary care but the model overestimates the risk.

Introduction

Cyclic nucleotide phosphodiesterases (PDEs) of the PDE4 subfamily are responsible for the hydrolysis and subcellular compartmentalization of cAMP, a second messenger that modulates vascular functionality. We had shown that PDE4B is induced in abdominal aortic aneurysms (AAA) and that PDE4 inhibition by rolipram limits experimental aneurysms. In this study we have delved into the mechanisms underlying the beneficial effect of rolipram on AAA.

Methods

AAA were induced in ApoE^−/− mice by angiotensin II (Ang II) infusion. Aneurysm formation was evaluated by ultrasonography. The expression of enzymes involved in redox homeostasis was analyzed by real-time RT-PCR and the activation of signaling pathways by Western blot.

Results

Induction of PDE4B in human AAA has been confirmed in a second cohort of patients. In Ang II-infused ApoE^−/− mice, rolipram increased the percentage of animals free of aneurysms without affecting the percentage of aortic ruptures. Quantitative analyses determined that this drug significantly attenuated aortic collagen deposition. Additionally, rolipram reduced the increased Nox2 expression triggered by Ang II, exacerbated Sod1 induction, and normalized Sod3 expression. Likewise, PDE4 inhibition decreased the activation of both ERK1/2 and the canonical Wnt pathway, while AKT activity was not altered.

Conclusions

The inhibition of PDE4 activity modulates the expression of enzymes involved in redox homeostasis and affects cell signaling pathways involved in the development of AAA.

Objective

The objective of the study is to describe the clinical and epidemiological characteristics of our patients with elevated Lp(a).

Materials and methods

A descriptive cross-sectional study was conducted on 316 patients with elevated Lp(a) (>125 nmol/L) in a random sample between January and August 2022. We measured epidemiological, anthropometric, clinical and laboratory variables (lipid metabolism parameters, carbohydrates and hormones).

Results

Mean age of our sample subject’s was 59 ± 15 years with 56% males. The average BMI was 27.6 kg/m² (71% with elevated BMI). Elevated waist circumference was observed in 54.1% of men and 77.8% of women. 48% had hypertension, 30.7% had diabetes mellitus and 91.5% dyslipidemia. Only 39.7% of the patients had never smoked.

The mean values of total cholesterol were 158 ± 45 mg/dl, LDL was 81 ± 39 mg/dl, HDL was 53 ± 17 mg/dl, Triglycerides were 127 ± 61 mg/dl, and Lp(a) was 260 ± 129 nmol/l.

Regarding lipid lowering treatment, 89% were on statins, 68.6% on ezetimibe, and 13.7% on PCSK9 inhibitors. 177 patients (57,7%) had established cardiovascular disease (CVD), 16.3% had polyvascular disease, 11.7% had subclinical CVD, and 30.6% had no known CVD. Among patients with established CVD, 174 (98.3%) were on lipid-lowering treatment (97.2% on statins) and 86.4% were on antiplatelet therapy. The mean age of cardiovascular events was 55 ± 12 years in males and 60 ± 11 years in females. 65,1% of female and 56,2% of male patients suffered an early cardiovascular event.

Conclusions

Patients with elevated Lp(a) are at very high cardiovascular risk, particularly for early cardiovascular disease.

Background

Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the Lipid Units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias.

Patients and methods

Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included.

Results

The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values ​​exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL.

Conclusions

Our results show an inverse Lp(a)-TG relationship in TG concentrations >300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

Background

The aim of this study was to investigate presence of subclinical atherosclerosis by measuring carotid intima-media thickness (CIMT) in patients with Helicobacter pylori (HP) and to assess effects of HP on atherosclerosis by evaluating markers of atherosclerosis and blood growth differentiation factor (GDF-15) levels.

Materials and methods

This cross-sectional study included 59 patients without comorbid disease who had HP and 30 healthy controls without HP in upper endoscopic biopsy. In order to assess atherosclerosis, the CIMT measurement was performed by sonography. Serum GDF-15 level was measured by ELISA method. In all patients, atherosclerosis markers were recorded. Atherogenic indices were calculated, including Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), plasma atherogenic index (PAI; log TG/HDL-c), non-HDL-c (TH-HDL-c) and atherogenic coefficient (AC; non-HDL-HDL-c).

Results

The GDF-15 level and CIMT were significantly higher in HP-positive group when compared to HP-negative group (p ≤ 0.001). There was a significant correlation between serum GDF-15 level and CIMT (r = 0.445; p ≤ 0.001). There was no correlation between other atherosclerosis markers and serum GDF-15 level or CIMT. The bacterial intensity on endoscopic specimen was only correlated with CIMT (p < 0.001). Vitamin B12 and D levels were comparable among groups.

Conclusion

This study suggested that there was a correlation between GDF-15 level and subclinical atherosclerosis development in patients with HP. However, GDF-15 level, which was found to be elevated while atherogenic indices were normal, can be an earlier marker for subclinical atherosclerosis.