Lipoprotein(a) [Lp(a)], discovered in 1963, has been associated with atherosclerotic cardiovascular disease (ASCVD) independent of other traditional risk factors, including LDL cholesterol. Lp(a) is an apolipoprotein B (apoB)-containing lipoprotein, which contains an LDL-like particle. Unlike LDL, which is a primary therapeutic target to decrease ASCVD, current guidelines recommend measuring Lp(a) for risk assessments because there is no clear evidence demonstrating the clinical benefit of decreasing Lp(a) using classical drugs such as niacin. However, recent Mendelian randomization studies indicate that Lp(a) causally correlates with ASCVD. In addition, novel drugs, including PCSK9 inhibitors, as well as antisense oligonucleotide for apo(a), have exhibited efficacy in decreasing Lp(a) substantially, invigorating a discussion whether Lp(a) could be a novel therapeutic target for further ASCVD risk reduction. This review aims to provide current understanding, and future perspectives, of Lp(a), which is currently considered a mere biomarker but may emerge as a novel therapeutic target in future clinical settings.
Enormous effort has been put into the prevention of atherosclerosis through risk modification, especially with lipid-lowering therapies. Regression, that is, the reversal of the atherosclerosis process, has long been a goal of atherosclerosis research among basic and clinical investigators. Intravascular ultrasound (IVUS) was developed in the 1990s as an intracoronary imaging technique to observe the details of the vessel walls and to measure the vessel lumen and plaque area with high reproducibility. Compared with the coronary angiogram, IVUS provides far more detailed information on the vessel wall. In this article, we review lipid-lowering trials that have used IVUS and discuss the current understanding of the effectiveness of aggressive lipid-lowering therapy, which inhibits atherosclerotic progression and induces regression and plaque stabilization.
Aim: The cardio–ankle vascular index (CAVI) represents the blood pressure-independent arterial stiffness from the origin of the aorta to the ankle. CAVI0 has been proposed as a variant index. We aimed to clarify the difference between CAVI and CAVI0 among large populations, and to explore reasons of the difference.
Methods: The subjects were 5,293 Japanese healthy and 3,338 hypertensive people. Simple and multiple regression analyses were performed using age, sex, body mass index, systolic, and diastolic blood pressure (Pd) as variables. Sub-group analysis was performed by sex and age. The CAVI values with and without adjustment by reference pressure were also compared.
Results: CAVI had a positive correlation with Pd, while CAVI0 had a negative correlation with Pd in the healthy population. The CAVI values of the hypertensive group were higher than those of healthy group in both men and women, but the CAVI0 values in women of the hypertensive group in the 30–39 age group was significantly lower than that of the corresponding healthy group. Differences of CAVI values with or without modification using the reference pressure were 1.09%±1.38% for the healthy group and 3.68%±1.66% for the hypertensive group.
Conclusion: CAVI showed the expected values, but CAVI0 showed inexplicable results in the healthy and hypertensive populations. The differences were due to the strong dependency of CAVI0 on Pd. Differences of CAVI values with or without reference pressure were negligible. These results indicate that CAVI obtained by the VaSera system is appropriate, but CAVI0 is not.
Aims: This study elucidates the association of macroangiopathy development in type 2 diabetes patients with various arteriosclerosis risk factors (ARFs) and results of cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI).
Methods: The correlation between current and past macroangiopathy development, with ARFs or CAVI/ABI data, was retrospectively analyzed using multivariate logistic regression in 816 patients with type 2 diabetes at a single center. C-statistics combining some independent variables selected using the stepwise method were evaluated.
Results: CAVI was significantly correlated with macroangiopathies, including coronary artery disease (CAD), arteriosclerosis obliterans (ASO), and stroke with odds ratios (OR) of 1.20, 1.22, and 1.19, respectively. ABI significantly correlated with ASO and stroke with respective OR of 13.6 and 2.47, but not with CAD. Areas under the receiver operating characteristic curves (ROCs) revealed the accuracy of detecting ASO and stroke was increased by the combination of CAVI＋ABI (0.94 and 0.74, respectively). However, areas under the ROC for the presence of CAD can be increased by the combination of CAVI and ARFs especially including dyslipidemia.
Conclusion: CAVI/ABI and some ARFs are useful tools in daily clinical care units to identify the current and past existence of macroangiopathy in patients with type 2 diabetes, but the prediction weights using these factors were different among CAD, ASO, and stroke.
Aims: Recent studies suggest elevated levels of small dense low-density lipoprotein cholesterol (sdLDL-C) can predict the risk of incident coronary heart disease (CHD), even in individuals considered to be at low risk for cardiovascular disease(CVD) based on their LDL-C levels. This study aims to prospectively investigate the association between sdLDL-C concentration and traditional and nontraditional CHD risk markers to explore the underlying roles of sdLDL-C in atherogenic processes.
Methods: Between 2009 and 2011, 594 healthy volunteers aged 35–65 years were recruited as control subjects in a study of work-related risk factors and acute CHD. All participants fasted for 12–14 h, and venous blood samples were collected in the morning to measure serum lipid profiles and other CHD-related markers. A standard oral glucose tolerance test was performed on all participants to assess their subclinical diabetes and prediabetes status.
Results: There were significantly positive associations between sdLDL-C concentration and traditional (age, smoking and alcohol drinking habit, blood pressure, body mass index (BMI), serum lipid profiles, and diabetes status) and nontraditional risk factors (complete blood counts, (CBC), fibrinogen, high-sensitivity C-reactive protein, and subclinical diabetes status) for CVD. After adjusting for confounding variables which include age, gender, BMI, hypertension, household income, and smoking and alcohol drinking habits, all atherosclerotic risk markers except D-dimer were significantly and positively associated with sdLDL-C.
Conclusions: Our data indicated sdLDL-C is strongly associated with atherosclerotic risk markers, such as inflammation, thrombosis, hematological markers, and prediabetes. This study supports the hypothesis that sdLDL-C is a promising CVD risk biomarker.
Aim: The study aimed to identify the underlying differentially expressed genes (DEGs) and mechanism of macrophage-enriched rupture atherosclerotic plaque using bioinformatics methods.
Methods: GSE41571, which includes six stable samples and five ruptured atherosclerotic samples, was downloaded from the GEO database. After preprocessing, DEGs between ruptured and stable atherosclerotic samples were identified using LIMMA. Gene Ontology biological process (GO_BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using the Database for Annotation, Visualization, and Integration Discovery (DAVID) online tool. Based on the STRING database, protein-protein interactions (PPIs) network among DEGs were constructed. Regulatory relationships between miRNAs/transcriptional factors (TFs) and target genes were predicted using Enrichr, and regulatory networks were visualized using Cytoscape.
Results: A total of 268 DEGs (64 up-regulated and 204 down-regulated DEGs) were identified between ruptured and stable samples. In the PPI network, collagen type III alpha 1 chain (COL3A1), collagen type I alpha 2 chain (COL1A2), and asporin (ASPN) were more than 15 interaction degrees. In the miRNA-target network, miR21 was highlighted with highest degrees and ASPN could be targeted by miR21. Functional enrichment analysis showed that COL3A1 and COL1A2 were significantly enriched in extracellular matrix organization and cell adhesion GO_BP terms. Pre-platelet basic protein (PPBP) was the most significantly up-regulated gene in ruptured atherosclerotic samples and enriched in immune response and inflammatory response GO_BP terms.
Conclusions: Down-regulated COL3A1, COL1A2 and ASPN, and up-regulated PPBP might perform critical promotional roles in atherosclerotic plaque rupture. Furthermore, miR21 might be potential target to prevent atherosclerotic rupture.
Aim: Cardio-ankle vascular index (CAVI) reflects arterial stiffness and has been established as a useful surrogate marker of atherosclerosis. Contrary to the abundant data indicating slower progression of atherosclerosis with statins, studies on fibrates remain scarce. The aim of this study was thus to clarify the effect of bezafibrate on CAVI as well as on oxidative stress.
Methods: A randomized, open-label, controlled study was performed. 66 hypertriglyceridemic patients with type 2 diabetes were assigned to two groups: bezafibrate (400 mg/day) group and eicosapentaenoic acid (EPA 1.8 g/day) group. Patients were administered the respective treatment for 12 weeks. CAVI, glycolipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs) were evaluated before and after the study period.
Results: Serum triglycerides (TG), remnant-like particle cholesterol (RLP-C), fasting plasma glucose, HbA1c and d-ROMs decreased, while HDL-cholesterol increased significantly in the bezafibrate group but did not change in the EPA group. The decreases in TG, RLP-C, HbA1c and d-ROMs were significantly greater in the bezafibrate group than in the EPA group. CAVI decreased significantly only in the bezafibrate group and the decrease was significantly greater in bezafibrate group than in EPA group. Simple regression analysis showed no significant relationship between the change in CAVI and changes in other variables. Multivariate logistic regression analysis identified high baseline CAVI, low HDL-cholesterol level, and bezafibrate administration as significant independent predictors of CAVI decrease.
Conclusion: Bezafibrate treatment ameliorates arterial stiffness accompanied by improvement of glycolipid metabolism and oxidative stress. These effects potentially have important beneficial health consequences in hypertriglyceridemic patients with type 2 diabetes.
Aim: The objective was to compare the rate of atrial fibrillation (AF) onset in patients with congenital heart disease (CHD) compared to controls.
Methods: Using a large number of samples extracted from nationwide cohort data in Taiwan, the authors used a propensity-matching procedure and multivariable Cox models to assess the risk of AF by CHD.
Results: A cohort of 19,439 CHD patients and a propensity-matched cohort of 19,439 control patients were included in this study. The cumulative incidence of AF was significantly higher in the CHD cohort than in the non-CHD cohort (p＜0.001). After controlling for confounding factors, the adjusted hazard ratio (aHR) of AF was 4.23 (95% confidence interval [CI] 3.31–5.41) in the CHD cohort, compared to the non-CHD cohort.
Conclusions: A significant association between CHD and AF risk was found.