Clinica e Investigacion en Arteriosclerosis最新文献

Epidemiologic evidence supported an inverse association between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major cardiovascular risk factor and postulating diverse HDL vascular- and cardioprotective functions beyond their ability to drive reverse cholesterol transport. However, the failure of several clinical trials aimed at increasing HDL-C in patients with overt cardiovascular disease brought into question whether increasing the cholesterol cargo of HDL was an effective strategy to enhance their protective properties. In parallel, substantial evidence supports that HDLs are complex and heterogeneous particles whose composition is essential for maintaining their protective functions, subsequently strengthening the “HDL quality over quantity” hypothesis.

The following state-of-the-art review covers the latest understanding as per the roles of HDL in ASCVD, delves into recent advances in understanding the complexity of HDL particle composition, including proteins, lipids and other HDL-transported components and discusses on the clinical outcomes after the administration of HDL-C raising drugs with particular attention to CETP (cholesteryl ester transfer protein) inhibitors.

Introduction

The lipid accumulation product (LAP) and visceral adipose index (VAI) are clinical markers of visceral obesity and were proposed as simple tools to estimate cardiovascular risk and mortality. The objective of this study was to analyze the accuracy of the VAI and LAP for high cardiovascular risk patients.

Methods

A cross-sectional observational study of accuracy was carried out in 193 patients of both sexes. In addition to the variables VAI and LAP, presence of comorbidities, education, level of physical activity and anthropometric data were obtained. Cardiovascular risk was determined by the Framingham score.

Results

No significant difference was observed in the sample in gender distribution (44.6% women; 55.4% men), 24.4% had low cardiovascular risk, 48.7% intermediate risk and 26.9% high cardiovascular risk. Linear regression analysis showed that VAI and LAP explain, respectively, only 2.4% and 5.2% of the variation in cardiovascular risk expressed by the Framingham score. The analysis of areas under the curve (AUC) for receiver operating characteristic (ROC) indicated a significant effect only of LAP to diagnose individuals with high cardiovascular risk, but with low sensitivity and specificity.

Conclusion

Our results indicate that VAI and LAP explain only a small percentage of the variation in the Framingham cardiovascular risk score. LAP index still deserves more attention in a cohort study, because, even with the limitations of a cross-sectional study, we observed an acceptable sensitivity for it so that the LAP can be used as a screening criterion for requesting more accurate tests.

In the management of hypercholesterolemia, besides advising a healthy, plant-based diet, it may be useful to recommend functional foods or nutraceutical with cholesterol-lowering properties. Given the progressive increase in the number of these products and their rising use by the population, the Spanish Society of Arteriosclerosis (SEA) has considered it appropriate to review the available information, select the results of the scientifically more robust studies and take a position on their usefulness, to recommend to health professionals and the general population their potential utility in terms of efficacy and their possible benefits and limitations. The following clinical scenarios have been identified in which these products could be used and will be analyzed in more detail in this document: (1) Hypolipidemic treatment in subjects with statin intolerance. (2) Hypolipidemic treatment «a la carte» in individuals in primary prevention. (3) Long-term cardiovascular prevention in individuals with no indication for lipid-lowering therapy. (4) Patients with optimized lipid-lowering treatment who do not achieve therapeutic objectives.

Primary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic disease. Among these, it is possible to differentiate between symptomatic and asymptomatic forms, in which, in the absence of secondary causes, the initial clinical suspicion is plasma ApoB levels below the 5 th percentile of the distribution by age and sex. Here we describe the differential diagnosis of a case of asymptomatic hypocholesterolemia. We studied proband's clinical data, the lipid profile of the proband and her relatives and the clinical data of the family relevant to carry out the differential diagnosis. We performed a genetic study as the diagnostic test. The information obtained from the differential diagnosis suggested a heterozygous hypobetalipoproteinemia due to PCSK9 loss-of-function variants. The diagnostic test revealed, in the proband, the presence of a heterozygous PCSK9 frame-shift variant of a maternal origin. Plasma levels of LDL cholesterol and PCSK9 of the patient and her relatives were compatible with the segregation of the variant revealed. In conclusion, the diagnostic test performed confirmed the suspected diagnosis of the proband as asymptomatic familial hypobetalipoproteinemia due to a loss-of-function variant in the PCSK9 gene.

Introduction and objective

The cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities.

Methods

Observational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited.

Results

Of the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P < .0001) in the achievement of target LDL-C < 70 and < 55 mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P = .0079).

Conclusions

Even though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy.

Background

APOE gene encoded a multifunctional protein in lipid metabolism, also associated with inflammatory markers. Type 2 diabetes (T2D) is a complex metabolic disease related to increased blood glucose, triglycerides and VLDL and associated with different dyslipidaemias. The aim of this study was to analyze whether the APOE genotype could determining the risk of developing T2D in a large cohort of workers.

Material and methods

Data from the Aragon Workers Health Study (AWHS) (n = 4895) were used to investigate the relationship between glycemic levels and APOE genotype. All patients in the AWHS cohort had their blood drawn after an overnight fast and laboratory tests were performed on the same day as the blood drawn. Dietary and physical assessment was assessed by face-to-face interview. APOE genotype was determined by the Sanger sequencing method.

Results

The relationship between APOE genotype and glycemic profile showed that glucose, Hb1Ac, insulin and HOMA levels did not seem to be associated with the APOE genotype (p = 0.563, p = 0.605, p = 0.333 and p = 0.276, respectively). In addition, the T2D prevalence did not show an association with the APOE genotype (p = 0.354). Along the same lines, blood glucose levels and T2D prevalence did not show association with the APOE allele. Shift work had some effect on the glycaemic profile, showing that night shift workers have significantly lower levels of glucose, insulin and HOMA (p < 0.001). However, the APOE genotype did not show difference in the concentration of glycaemic parameters adjusting by sex, age and BMI, work shift and dietary parameters.

Conclusion

Glycemic profile and T2D prevalence did not show any significant association with the APOE genotype. Besides, individuals, who worked in non-rotating night shift showed significantly lower glycemic levels, while workers in the morning-afternoon-night shift showed significantly higher values.

Introduction

Abdominal aortic aneurysm (AAA) is a multifactorial, degenerative disease characterized by progressive aortic dilation and chronic activation of inflammation, proteolytic activity, and oxidative stress in the aortic wall. The immune response triggered by antibodies against antigens present in the vascular wall participates in the formation and progression of AAA through mechanisms not completely understood. This work analyses the function of specific IgG receptors (FcγR), especially those expressed by monocytes/macrophages, in the development of experimental AAA.

Methods

In the elastase-induced AAA model, the abdominal aortas from wildtype and FcγR deficient mice with/without macrophage adoptive transfer were analysed by histology and quantitative PCR. In vitro, mouse macrophages were transfected with RNA interference of FcγRIV/CD16.2 or treated with Syk kinase inhibitor before stimulation with IgG immune complexes.

Results

Macrophage adoptive transfer in FcγR deficient mice increased the susceptibility to AAA development. Mice receiving macrophages with functional FcγR exhibited higher aortic diameter increase, higher content of macrophages and B lymphocytes, and upregulated expression of chemokine CCL2, cytokines (TNF-α and IL-17), metalloproteinase MMP2, prooxidant enzyme NADPH oxidase-2, and the isoforms FcγRIII/CD16 and FcγRIV/CD16.2. In vitro, both FcγRIV/CD16.2 gene silencing and Syk inhibition reduced cytokines and reactive oxygen species production induced by immune complexes in macrophages.

Conclusions

Activation of macrophage FcγR contributes to AAA development by inducing mediators of inflammation, proteolysis, and oxidative stress. Modulation of FcγR or effector molecules may represent a potential target for AAA treatment.

We present cardiovascular disease (CVD) incidence and mortality rates reported for South America stratified by country, sex, and urban/rural location in a multinational cohort included in the Population Urban Rural Epidemiological Study (PURE). This study included 24,718 participants from 51 urban and 49 rural communities in Argentina, Brazil, Chile, and Colombia and the mean follow-up was 10.3 years. CVD incidence and mortality rates were calculated for the total cohort and in subpopulations. Hazard ratios and population attributable fractions (PAFs) for CVD and death were examined for 12 modifiable risk factors, grouped as metabolic (hypertension, diabetes, abdominal obesity, and high non-HDL cholesterol), behavioural (smoking, alcohol, diet quality, and physical activity) and other (education, household air pollution, strength, and depression). The leading causes of death were CVD (31.1%), cancer (30.6%), and respiratory diseases (8.6%). Approximately 72% of the PAFs for CVD and 69% of the PAFs for deaths were attributed to 12 modifiable risk factors. For CVD, the main PAFs were due to hypertension (18.7%), abdominal obesity (15.4%), smoking (13.5%), low muscle strength (5.6%), and diabetes (5.3%). For death, the main PAFs were smoking (14.4%), hypertension (12.0%), low educational level (10.5%), abdominal obesity (9.7%), and diabetes (5.5%). Cardiovascular diseases, cancer, and respiratory diseases account for more than two-thirds of deaths in South America. Men have consistently higher CVD rates and mortality than women. A large proportion of CVD and premature deaths could be avoided by controlling metabolic risk factors and smoking, which are the main risk factors in the region for both CVD and all-cause mortality.