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Background Despite continuous improvements of diagnostic and therapeutic algorithms for cardiovascular disease (CVD), mortality from CVD remains high suggesting unaddressed residual risk. Remnant cholesterol (RC) consists the cholesterol content of triglyceride-rich lipoproteins, which along with LDL cholesterol infiltrate the arterial wall, accumulate and cause atherosclerosis. Increased remnant cholesterol (RC) levels have been previously associated with future adverse cardiac events despite hypolipidemic therapy. However, a mechanistic association of RC levels with human atherosclerosis in vivo has not been proven in a clinical setting. Purpose To evaluate the association of RC levels with the presence and extend of subclinical carotid atherosclerosis. Methods In this retrospective cohort study, 438 subjects from the Athens Vascular Registry without clinically overt CVD or treatment with statin were recruited. Atherosclerotic burden was assessed by B-mode carotid ultrasonography using: 1. Maximal carotid wall thickness [maxWT, the highest intima-media thickness (IMT) or highest atherosclerotic plaque thickness (PLQ) if present derived from all carotid sites], 2. Total thickness (sumWT, sum of maximal wall thickness), 3) high plaque burden (PLQ ≥2) and 4) average carotid IMT (avgIMT). RC was calculated using the formula RC=total cholesterol-LDL-C-HDL-C. Results Mean (SD) age was 54.8±12.4 years old with 41% being males. Subjects with RC>median (=18mg/dl) had higher sumWT (6.12±0.7 vs 5.57±1.7, p=0.002), maxWT (1.61±0.7 vs 1.43±0.7, p=0.008) and avgIMT (0.88±0.16 vs 0.83±0.16, p=0.003) vs RCmedian was associated with higher odds for increased sumWT (highest tertile, OR: 2.15 95% CI 1.26–3.66, p=0.006) and maxWT (OR: 2.15 95% CI: 1.38–3.33, p=0.001), and a higher plaque burden (≥2 plaques, OR: 2.1 95% CI 1.93–3.1, p Conclusion In a statin-naive population without clinically overt CVD, increased RC levels were associated with the presence and extend of subclinical carotid atherosclerosis. These findings provide novel mechanistic insight into mechanisms associated with increased CVD risk in individuals with high RC levels. Funding Acknowledgement Type of funding sources: None.

Background Among high cardiovascular (CV) risk patients, there is emerging need to recognize those who will benefit from new treatments targeting residual risk. Readily available modalities providing reclassification value would be clinically useful in this setting. Preliminary data suggest that carotid ultrasonography using plaque burden but not intima-media thickness (IMT) is associated with very high risk. Objectives We aimed to assess the reclassification ability of two markers of carotid atherosclerosis in high-risk patients, reflecting total atherosclerotic burden and the most severe lesion and to compare them with the routinely used carotid indices IMT and number of carotid plaques. Methods In an ongoing registry of patients who visited a cardiovascular protection clinic for cardiovascular risk assessment, we enrolled 735 consecutively recruited patients (mean age 63.1 years, 68.8% male) classified as high or very-high CV risk according to 2019 European Society of Cardiology /European Atherosclerosis Society Guidelines. Sum of carotid wall thickness (sumWT) and maximal wall thickness (maxWT) using high-resolution ultrasonography at baseline were used to assess the total burden and the most severe carotid lesion, respectively. These markers integrate maximum plaque height or maximum IMT if no plaque is present. All patients were followed for a median of 41 months and the primary end-point consisted of CV mortality, acute myocardial infarction or coronary revascularization. Results After adjustment for traditional CV risk factors, maxWT and sumWT were associated with the primary end-point (hazard ratio [HR]=1.73 (95% confidence interval [CI]:1.39 to 2.17) and 1.19 (95% CI 1.10 to 1.30) respectively). Both markers were superior in terms of reclassification and discrimination to identify very high risk over validated CV risk scores including the Heartscore and the SMART score (net reclassification index [NRI]=0.624, p Conclusions The use of two novel cumulative markers of atherosclerotic burden improves risk stratification and discriminates high from very high CV risk. Given that carotid ultrasonography is a readily available modality, its clinical application for risk refinement of high-risk patients to facilitate treatment decisions merits further investigation. Funding Acknowledgement Type of funding sources: None.

SARS-CoV-2 (Covid-19) infection has recently become a worldwide challenge with dramatic global economic and health consequences. As the pandemic is still spreading, new data concerning Covid-19 complications and related mechanisms become increasingly available. Accumulating data suggest that the incidence of cardiac arrest and its outcome are adversely affected during the Covid-19 period. This may be further exacerbated by drug-related cardiac toxicity of Covid-19 treatment regimens. Elucidating the underlying mechanisms that lead to Covid-19 associated cardiac arrest is imperative, not only in order to improve its effective management but also to maximize preventive measures. Herein we discuss available epidemiological data on cardiac arrest during the Covid-19 pandemic as well as possible associated causes and pathophysiological mechanisms and highlight gaps in evidence warranting further investigation. The risk of transmission during cardiopulmonary resuscitation (CPR) is also discussed in this review. Finally, we summarize currently recommended guidelines on CPR for Covid-19 patients including CPR in patients with cardiac arrest due to suspected drug-related cardiac toxicity in an effort to underscore the most important common points and discuss discrepancies proposed by established international societies., Highlights • Covid-19 pandemic is associated with increased incidence of cardiac arrest. • Cardiac, non-cardiac causes and drug-related toxicity may jointly contribute to cardiac arrest associated with Covid-19. • Recommendations for cardiac arrest management are modified during the pandemic. • Recommendations for prevention and management of drug-related toxicity related to Covid-19 are summarized.