Circulating MicroRNAs as Novel Diagnostic Biomarkers for Very Early-onset(≤40 years) Coronary Artery Disease

Objective Very early-onset coronary artery disease （CAD） is a great challenge in cardiovascular medicine throughout the world, especially regarding its early diagnosis. This study explored whether circulating microRNAs （miRNAs） could be used as potential biomarkers for patients with very early-onset CAD. Methods We performed an initial screening of miRNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age- and sex-matched normal controls. For further confirmation, we prospectively examined the miRNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls. Results A total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysis of the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p exhibited significantly decreased expression in patients compared with that in controls （P〈0.05）. The areas under the receiver operating characteristic curve for these miRNAs were 0.824 （95% CI, 0.731-0.917; P〈0.001）, 0.758 （95% CI, 0.651-0.864; P〈0.001）, 0.753 （95% CI, 0.643-0.863; P〈0.001）, and 0.782 （95% CI, 0.680-0.884; P〈0.001）, respectively, in the validation set. Conclusion To our knowledge, this is an advanced study to report about four serum miRNAs （miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p） that could be used as novel biomarkers for the diagnosis of very early-onset CAD.

Impact of Smoking Status on Lipoprotein Subfractions： Data from an Untreated Chinese Cohort

Objective Cigarette smoking is one of the established risk factors of atherosclerotic cardiovascular disease, however, its impact on lipids is not completely understood, especially in the Chinese population. Therefore, this study evaluated the impact of smoking status （non, former, and current smoking） on the distribution of lipoprotein subfractions in untreated patients with angina-like chest pain. Methods A total of 877 patients were consecutively enrolled and divided into nonsmoking （n = 528）, former smoking （n = 103）, and current smoking （n = 256） groups. Both low- and high-density lipoprotein cholesterol （LDL-C and HDL-C） subfractions were measured using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated among the groups. Results Compared with nonsmoking subjects, the current smoking group had significantly lower large/medium HDL-C （both P 〈 0.001） concentration and large HDL subfraction percentage but higher small HDL-C and medium LDL-C concentrations as well as medium LDL subfraction percentage. Importantly, former smoking subjects showed elevated levels of large HDL-C concentration, large HDL particle percentage, and mean LDL particle size and attenuation in small HDL/LDL percentages and small LDL-C concentration, but these levels did not reach the optimal status compared with those of the non-smoking group （data not shown）. Conclusion Smoking has an adverse impact on the lipoprotein subfractions, presented as lower large HDL particles besides higher small HDL and medium LDL particles, whereas smoking cessation could reverse these change to a certain degree.

Lipoprotein(a) as a Marker for Predicting the Presence and Severity of Coronary Artery Disease in Untreated Chinese Patients Undergoing Coronary Angiography

Objective Low-density lipoprotein cholesterol（LDL-C） has been well known as the risk factor of coronary artery disease（CAD）. However, the role of lipoprotein（a） [Lp（a）] in the development of CAD is of great interest but still controversial. Thus, we aim to explore the effect of Lp（a） on predicting the presence and severity of CAD in Chinese untreated patients, especially in combination with LDL-C. Methods We consecutively recruited 1,980 non-treated patients undergoing coronary angiography, among which 1,162 patients were diagnosed with CAD. Gensini score（GS） was used to assess the severity of CAD. Lp（a） was measured by immunoturbidimetric method. Results Patients with CAD had higher level of LDL-C and Lp（a） compared with non-CAD（P 〈 0.05）. Multivariable logistic regression revealed that Lp（a） 〉 205 mg/L（highest tertile） predicted 1.437-fold risk for CAD（95% CI： 1.108-1.865, P = 0.006） and 1.480-fold risk for high GS（95% CI： 1.090-2.009, P = 0.012） respectively. Interestingly, concomitant elevated level of Lp（a） and LDL-C conferred the highest risk for both presence [OR = 1.845, 95% CI： 1.339-2.541, P 〈 0.001] and severity [OR = 1.736, 95% CI： 1.188-2.538, P = 0.004] of CAD. Conclusion Lipoprotein（a） is a useful marker for predicting the presence and severity of CAD, especially combined with LDL-C.

Plasma apo CⅢ Levels in Relation to Inflammatory Traits and Metabolic Syndrome in Patients not Treated with Lipid-lowering Drugs Undergoing Coronary Angiography

Objective Assessment of the comprehensive relationship among apolipoprotein CIII（apoCⅢ） levels, inflammation, and metabolic disorders is rare. Methods A total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCⅢ in the association of inflammation with metabolic syndrome（MetS）. Results Patients with MetS showed higher levels of apoCⅢ [95.1（73.1-131.4） vs. 81.7（58.6-112.4） μg/mL, P 〈 0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7（0.8-3.4） vs. 1.1（0.5-2.2） mg/L; white blood cell count,（6.48 ± 1.68） vs.（6.11 ± 1.67） × 10~9/L]. The levels of apoCⅢ and inflammatory markers increased with the number of metabolic risk components（all P 〈 0.001）. Furthermore, apoCⅢ levels were associated with virtually all individual MetS risk factors and inflammatory markers（all P 〈 0.05）. Importantly, the prevalence of MetS in each metabolic disorder rose as apoCⅢ levels increased（all P 〈 0.05）. Mediation analysis showed that apoCⅢ partially mediated the effect of inflammation on MetS independently from triglycerides. Conclusion Plasma apoCⅢ levels were significantly associated with the development and severity of MetS, and a role of apoCⅢ in the effect of inflammation on the development of MetS was identified.