The metabolic syndrome is a complex disorder unifying dyslipidemia, insulin resistance, and hypertension. It is a primary risk factor for diabetes¹ and cardiovascular disease.² The overall prevalence of metabolic syndrome as defined by Adult Treatment Panel III guidelines³ in US adults is high (22%), and even higher among older men and women (42%).⁴ Physical inactivity, obesity, and diet composition all appear to be risk factors for the development of the metabolic syndrome.⁵ However, little is known concerning risk factors of the metabolic syndrome specific to older adults, who have a higher incidence of type 2 diabetes^6,7 and cardiovascular disease⁸ than younger adults.

Background —The association between oxidative modifications of LDL and coronary artery disease (CAD) is suspected but not established. Therefore, the association between plasma levels of oxidized LDL and malondialdehyde (MDA)-modified LDL and acute coronary syndromes and stable CAD was investigated. Methods and Results —The study population contained 63 patients with acute coronary syndromes (45 with acute myocardial infarction and 18 with unstable angina pectoris), 35 nontransplanted patients with angiographically confirmed stable angina, 28 heart transplant patients with posttransplant CAD, 79 heart transplant patients without CAD, and 65 control subjects. After correction for age, sex, and LDL and HDL cholesterol, plasma levels of oxidized LDL and MDA-modified LDL were significantly higher in patients with CAD than in individuals without CAD ( r ² =0.57 and r ² =0.26, respectively; both P =0.0001). Plasma levels of MDA-modified LDL were significantly higher in patients with acute coronary syndromes than in individuals with stable CAD ( r ² =0.65; P =0.0001) and were associated with increased levels of troponin I and C-reactive protein ( r ² =0.39 and r ² =0.34, respectively; both P =0.0001). Plasma levels of oxidized LDL were not associated with increased levels of troponin I and C-reactive protein ( r ² =0.089 and r ² =0.063, respectively). Conclusions —Elevated plasma levels of oxidized LDL are associated with CAD. Elevated plasma levels of MDA-modified LDL suggest plaque instability and may be useful for the identification of patients with acute coronary syndromes.

Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors—mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current ‘state of the art’ on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future research.

—Our aim was to determine the usefulness of circulating oxidized low density lipoprotein (LDL) in the identification of patients with coronary artery disease (CAD). A total of 304 subjects were studied: 178 patients with angiographically proven CAD and 126 age-matched subjects without clinical evidence of cardiovascular disease. The Global Risk Assessment Score (GRAS) was calculated on the basis of age, total and high density lipoprotein cholesterol, blood pressure, diabetes mellitus, and smoking. Levels of circulating oxidized LDL were measured in a monoclonal antibody 4E6–based competition ELISA. Compared with control subjects, CAD patients had higher levels of circulating oxidized LDL ( P <0.001) and a higher GRAS ( P <0.001). The sensitivity for CAD was 76% for circulating oxidized LDL (55% for men and 81% for women) compared with 20% (24% for men and 12% for women) for GRAS, with a specificity of 90%. Logistic regression analysis revealed that the predictive value of oxidized LDL was additive to that of GRAS ( P <0.001). Ninety-four percent of the subjects with high (exceeding the 90th percentile of distribution in control subjects) circulating oxidized LDL and high GRAS had CAD (94% of the men and 100% of the women). Thus, circulating oxidized LDL is a sensitive marker of CAD. Addition of oxidized LDL to the established risk factors may improve cardiovascular risk prediction.

The aim of the present study is to identify microRNAs (miRs) with high potential to be used as biomarkers in plasma and/or serum to clinically diagnose, or provide accurate prognosis for survival in, patients with atherosclerosis, coronary artery disease, and acute coronary syndrome (ACS). A systematic search of published original research yielded a total of 72 studies. After review of the risk of bias of the published studies, according to Cochrane Collaboration and the QUADUAS Group standards, 19 studies were selected. Overall 52 different miRs were reported. In particular, miR-133a/b (5 studies), miR-208a/b (6 studies), and miR-499 (7 studies) were well studied and found to be significant diagnostic and/or prognostic markers across different cardiovascular disease progression stages. miR-1 and miR-145b are potential biomarkers of ACS; miR-1 with higher sensitivity for all acute myocardial infarction (AMI), and miR-145 for STEMI and worse outcome of AMI. But when miRs were studied across different ACS study populations, patients had varying degrees of coronary stenosis, which was identified as an important confounder that limited the ability to quantitatively pool the study results. The identified miRs were found to regulate endothelial function and angiogenesis (miR-1, miR-133), vascular smooth muscle cell differentiation (miR-133, miR-145), communication between vascular smooth muscle and endothelial cell to stabilize plaques (miR-145), apoptosis (miR-1, miR-133, miR-499), cardiac myocyte differentiation (miR-1, miR-133, miR-145, miR-208, miR-499), and to repress cardiac hypertrophy (miR-133). Their role in these processes may be explained by regulation of shared RNA targets such as cyclin-dependent kinase inhibitor 1A (or p21), ETS proto-oncogene 1, fascin actin-bundling protein 1, hyperpolarization-activated cyclic nucleotide-gated potassium channel 4, insulin-like growth factor 1 receptor LIM and SH3 protein 1, purine nucleoside phosphorylase, and transgelin 2. These mechanistic data further support the clinical relevance of the identified miRs. miR-1, miR-133a/b, miR-145, miR-208a/b, and miR-499(a) in plasma and/or serum show some potential for diagnosis of cardiovascular disease. However, biased selection of miRs in most studies and unexplained contrasting results are major limitations of current miR research. Inconsistencies need to be addressed in order to definitively identify clinically useful miRs. Therefore, this paper presents important aspects to improve future miR research, including unbiased selection of miRs, standardization/normalization of reference miRs, adjustment for patient comorbidities and medication, and robust protocols of data-sharing plans that could prevent selective publication and selective reporting of miR research outcomes.