Aortic calcification is associated with coronary artery calcification and is a potential surrogate marker for ischemic heart disease risk: A cross-sectional study.

Coronary artery calcification, an established marker of atherosclerotic plaque burden associated with increased risk of coronary artery disease, is routinely evaluated using electron beam computerized tomography or multidetector computed tomography (CT). However, aortic calcification, which is also a risk factor for adverse cardiac events, is not frequently assessed, despite being easily detected via standard chest radiography. We therefore sought to clarify the association between aortic calcification and significant coronary artery calcification to determine the feasibility of performing chest radiography to evaluate the risk of future cardiovascular events. Data from 682 consecutive patients who underwent cardiac CT scanning at our institution from May to September 2012 were included in this cross-sectional analysis. Electrocardiographic-gated CT was used to qualitatively evaluate calcification in 6 aortic segments. Cardiac contrast-ehnanced CT was performed to identify significant calcification of the coronary artery. Calcification was quantified by calculating the Agatston score, and the relationship between significant coronary artery calcification and calcification at each aortic site was evaluated. Among the aortic sites, calcification was most commonly observed in the aortic arch (77.4% of patients). Significant coronary artery calcification was observed in 267 patients (39.1%). Calcification in the ascending aorta, aortic arch, descending aorta, abdominal aorta, and aortic valve were significantly associated with the presence of coronary artery calcification after adjustment for cardiovascular risk factors and statin use (odds ratios [95% confidence intervals] 4.21 [2.55, 6.93], 1.65 [1.01, 2.69], 2.14 [1.36, 3.36], 2.87 [1.83, 4.50], and 3.32 [2.02, 5.46], respectively). Mitral valve calcification was weakly but nonsignificantly associated with coronary artery calcification (odds ratio 1.84 [95% confidence interval 0.94, 3.62]). Calcification of each aortic segment assessed was significantly associated with Agatston score ≥ 100. Aortic calcification was associated with coronary artery calcification. Calcification of the aortic arch, which can be readily detected by routine chest radiography, may be associated with coronary artery calcification and its assessment should therefore be considered to identify patients at increased risk of cardiovascular events. Further studies are warranted to confirm these findings.

Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial.

Importance: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. Objective: To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. Design, Setting, and Participants: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. Interventions: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. Results: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, -1.34% [95% CI, -2.57% to -0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, -0.55% [95% CI, -1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, -1.13% [95% CI, -1.84% to -0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). Conclusions and Relevance: Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02619760.

Impact of hypertriglyceridemia on endothelial dysfunction during statin ± ezetimibe therapy in patients with coronary heart disease.

Despite the use of statin therapy and achieving the target for low-density lipoprotein cholesterol, a substantial number of coronary events are not prevented, and residual risk factors remain unsettled. Recently, ezetimibe has been shown to reduce not only low-density lipoprotein cholesterol but also triglyceride (TG) levels. The aim of this study was to investigate the associations of residual risk factors, mainly hypertriglyceridemia, with endothelial function during statin therapy in patients with coronary heart disease and examine the effect of ezetimibe add-on therapy. A total of 109 consecutive patients with coronary heart disease during statin therapy were enrolled. Lipid profile was measured and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery in a fasting state. Next, 32 patients with high TG levels (≥150 mg/dl) were prospectively assigned to the ezetimibe add-on group or the no-ezetimibe group, and endothelial function was assessed after 3 months. Multivariate linear regression analysis demonstrated that serum TG and high-density lipoprotein cholesterol levels were independent determinants of percentage FMD (ß = -0.210 and 0.208, respectively, p <0.05). In patients with high TG levels, ezetimibe add-on therapy significantly improved percentage FMD (from 3.3 ± 1.1% to 4.0 ± 1.1%, p <0.005), whereas no significant change was observed in the no-ezetimibe group. Moreover, the improvement in percentage FMD was significantly associated with reduction in serum TG levels (ß = -0.387, p <0.05) independent of the change in serum low-density lipoprotein cholesterol levels. In conclusion, hypertriglyceridemia is independently associated with endothelial dysfunction in patients with coronary heart disease during statin therapy. Ezetimibe add-on therapy improves endothelial function in these high-risk populations.

Elevated oxidative stress is associated with ventricular fibrillation episodes in patients with Brugada-type electrocardiogram without SCN5A mutation.

BACKGROUND: Brugada syndrome is a disease known to cause ventricular fibrillation with a structurally normal heart and is linked to SCN5A gene mutation. However, the mechanism by which ventricular fibrillation develops in cases of Brugada-type electrocardiogram without SCN5A mutation has remained unclear. Recently, oxidative stress has been implicated in the pathophysiology of cardiac arrhythmia. We also investigated oxidative stress levels in the myocardia of patients with Brugada-type electrocardiogram. METHODS: Endomyocardial biopsy samples were obtained from 68 patients with Brugada-type electrocardiogram (66 males and two females). We performed histological and immunohistochemical analyses for CD45, CD68, and 4-hydroxy-2-nonenal-modified protein, which is a major lipid peroxidation product. RESULTS: SCN5A mutation was detected in 14 patients. Ventricular fibrillation was documented in three patients with SCN5A mutation and in 11 without SCN5A mutation. In patients with SCN5A mutation, 4-hydroxy-2-nonenal-modified protein-positive area was not significantly different between the documented ventricular fibrillation (VF) group (VF+ group) and the group without documented VF (VF- group). However, in patients without SCN5A, the area was significantly larger in the VF+ group than that in the VF- group (P<.05). All other parameters (fibrosis area, CD45, and CD68) were not different between the VF+ and VF- group in both SCN5A+ and SCN5A- patients. CONCLUSION: Oxidative stress is elevated in the myocardium of patients with Brugada-type electrocardiogram who have VF episodes and do not have SCN5A gene mutations. Oxidative stress may be associated with the occurrence of VF in patients with Brugada-type electrocardiogram without SCN5A mutation.