Clinica e Investigacion en Arteriosclerosis最新文献

Introduction

Cardiovascular calcification is an important public health issue with an unmeet therapeutic need. We had previously shown that lysyl oxidase (LOX) activity critically influences vascular wall smooth muscle cells (VSMCs) and valvular interstitial cells (VICs) calcification by affecting extracellular matrix remodeling. We have delved into the participation of LOX in atherosclerosis and vascular calcification, as well as in the mineralization of the aortic valve.

Methods

Immunohistochemical and expression studies were carried out in human atherosclerotic lesions and experimental models, valves from patients with aortic stenosis, VICs, and in a genetically modified mouse model that overexpresses LOX in CMLV (TgLOX^CMLV). Hyperlipemia and atherosclerosis was induced in mice through the administration of adeno-associated viruses encoding a PCSK9 mutated form (AAV-PCSK9^D374Y) combined with an atherogenic diet.

Results

LOX expression is increased in the neointimal layer of atherosclerotic lesions from human coronary arteries and in VSMC-rich regions of atheromas developed both in the brachiocephalic artery of control (C57BL/6J) animals transduced with PCSK9^D374Y and in the aortic root of ApoE^−/− mice. In TgLOX^CMLV mice, PCSK9^D374Y transduction did not significantly alter the enhanced aortic expression of genes involved in matrix remodeling, inflammation, oxidative stress and osteoblastic differentiation. Likewise, LOX transgenesis did not alter the size or lipid content of atherosclerotic lesions in the aortic arch, brachiocephalic artery and aortic root, but exacerbated calcification. Among lysyl oxidase isoenzymes, LOX is the most expressed member of this family in highly calcified human valves, colocalizing with RUNX2 in VICs. The lower calcium deposition and decreased RUNX2 levels triggered by the overexpression of the nuclear receptor NOR-1 in VICs was associated with a reduction in LOX.

Conclusions

Our results show that LOX expression is increased in atherosclerotic lesions, and that overexpression of this enzyme in VSMC does not affect the size of the atheroma or its lipid content, but it does affect its degree of calcification. Further, these data suggest that the decrease in calcification driven by NOR-1 in VICs would involve a reduction in LOX. These evidences support the interest of LOX as a therapeutic target in cardiovascular calcification.

Introduction and objectives

Lipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease, and to assess its influence on the achievement of LDL-C targets.

Method

We conducted a cross-sectional study in a cardiology department in Spain. A total of 870 patients with stable coronary artery disease had their lipid profile determined, including Lp(a). Patients were stratified into 2 groups according to Lp(a) > 50 mg/dL and Lp(a) ≤ 50 mg/dL. The association of Lp(a) > 50 mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis.

Results

The prevalence of Lp(a) > 50 mg/dL was 30.8%. Patients with Lp(a) > 50 mg/dL had higher baseline (142.30 ± 47.54 vs. 130.47 ± 40.75 mg/dL; p = 0.0001) and current (72.91 ± 26.44 vs. 64.72 ± 25.30 mg/dL; p = 0.0001), despite the fact that they were treated with more high-potency statins (77.2 vs. 70.9%; p = 0.058) and more combination lipid-lowering therapy (37.7 vs. 25.7%; p = 0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a) > 50 mg/dL. Independent predictors of having elevated Lp(a) levels > 50 mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08-2.14), combination lipid-lowering therapy with ezetimibe (OR 2.0; 95% CI 1.45-2.73) and failure to achieve a LDL-C ≤55 mg/dL (OR 2.3; 95% CI 1.63-3.23).

Conclusions

Elevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients.

Introduction

The aim of this study was to investigate the relationship between the dietary oxidative balance score (OBS), an indicator of oxidative stress, anthropometric measures and socioeconomic factors in women at low risk of cardiovascular disease.

Methods

The participants’ 3-day dietary intake, demographic information, anthropometric measurements and blood pressure values were recorded, and the Framingham Risk Score (FRS) and OBS values were determined. Oxidative balance score consists of prooxidant and antioxidant scores. Prooxidant scores were calculated from red meat consumption, total iron and polyunsaturated fatty acid intake, alcohol and cigarette consumption parameters, while antioxidant scores were calculated by assessing cruciferous consumption, dietary total vitamin C, vitamin E, β-carotene, β-cryptoxanthin, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin and selenium intake.

Results

A total of 145 women were included in the study. Education level was associated with anthropometric measurements, income status with antioxidant and prooxidant scores, and exercise status with OBS (p < 0.05). Weight, waist, hip, BMI, waist/hip, and waist/height ratio were significantly lower in subjects with low prooxidant score (p < 0.05); there was no significant relationship between age, systolic, diastolic, FRS (p > 0.05).

Conclusion

The study, conducted in healthy women, showed that dietary oxidative balance scoring is promising in preventing the development of CVD and reducing the burden of disease, and that prospective cohort studies should be conducted in this area.

Imaging is instrumental in diagnosing and directing the management of atherosclerosis. In 1958 the first diagnostic coronary angiography (CA) was performed, and since then further development has led to new methods such as coronary CT angiography (CTA), optical coherence tomography (OCT), positron tomography (PET), and intravascular ultrasound (IVUS). Currently, CA remains powerful for visualizing coronary arteries; however, recent studies show the benefits of using other non-invasive techniques. This review identifies optimum imaging techniques for diagnosing and monitoring plaque stability. This becomes even direr now, given the rapidly rising incidence of atherosclerosis in society today. Many acute coronary events, including acute myocardial infarctions and sudden deaths, are attributable to plaque rupture. Although fatal, these events can be preventable. We discuss the factors affecting plaque integrity, such as increased inflammation, medications like statins, and increased lipid content. Some of these precipitating factors are identifiable through imaging. However, we also highlight significant complications arising in some modalities; in CA this can include ventricular arrhythmia and even death. Extending this, we elucidated from the literature that risk can also vary based on the location of arteries and their plaques. Promisingly, there are less invasive methods being trialled for assessing plaque stability, such as Cardiac Magnetic Resonance Imaging (CMR), which is already in use for other cardiac diseases like cardiomyopathies. Therefore, future research focusing on using imaging modalities in conjunction may be sensible, to bridge between the effectiveness of modalities, at the expense of increased complications, and vice versa.

Background

Teleconsultation in the context of clinical laboratories is a valuable tool for the early detection of dyslipidemia and prevention of cardiovascular risk. Here, we describe a patient who was referred to the Lipid Unit of the Virgen Macarena Hospital due to an alert for severe hypertriglyceridemia through its teleconsultation program.

Case presentation

A comprehensive clinical and biochemical study of the patient was carried out, and genetic testing was performed on the patient and his family. The proband and his family showed mild to severe hypertriglyceridemia and various secondary factors, together with a genetic background associated with a triglyceride-raising effect.

Conclusion

This extensive study has identified a family at high risk of cardiovascular disease and acute pancreatitis. These findings can help maximize lifestyle changes and improve the clinical management of their dyslipidemia.

Patients with obstructive sleep apnea (OSA) experience repetitive episodes of upper airway obstruction due to recurrent collapse during sleep. This leads to intermittent hypoxia episodes, which, through complex pathophysiological mechanisms, trigger sympathetic overactivation, endothelial dysfunction, hypercoagulation, and metabolic dysregulation. Consequently, other cardiovascular risk factors such as hypertension, metabolic syndrome, and diabetes are induced. Furthermore, this enhances target organ damage, affecting the heart, arteries, and kidneys, leading to an increased risk of cardiovascular morbidity and mortality. Among the various treatments for OSA, Continuous Positive Airway Pressure (CPAP) has been extensively studied. To date, this treatment has shown mild benefits in reducing blood pressure, particularly noticeable in patients with resistant hypertension. Furthermore, CPAP treatment appears to reduce cardiovascular events, both in primary and secondary prevention, though this benefit is limited to individuals with good compliance (CPAP use ≥4h/night). Future research perspectives in OSA seem to focus on identifying patients in whom the condition significantly influences cardiovascular risk, thus determining those who would benefit the most from treatment in the reduction of cardiovascular risk.