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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.

The impact of physical exercise, as preventative measure, to control the progression of cardiovascular disease in midlife remains under investigation. We aimed to investigate the effect of different levels of intensity of physical activity on metabolic and vascular profile in healthy postmenopausal women. A total of 625 healthy postmenopausal women (mean age 57.7 ± 7.6 years) were evaluated using the short IPAQ questionnaire for quantification of physical activity. The energy expenditure was estimated in metabolic equivalent of energy (MET) hours per week. Pulse wave velocity (PWV) was measured as an index of arterial stiffness. Intima-media thickness of both right and left common carotid artery, carotid bulb and internal carotid artery, and combined carotid IMT were also assessed by non-invasive and well-validated methods. Mean values of PWV decreased linearly with increasing intensity of physical activity (classes of physical activity: sedentary vs walking vs moderate vs vigorous activity: 9.07 ± 1.22 m/s vs 9.12 ± 1.72 m/s vs 8.47 ± 1.31m/s vs 7.94 ± 0.40 m/s, ANOVA P for linear trend .003). In non-obese postmenopausal women, PWV values associated with: (a) the total number of METs (b-coefficient = -0.261, P = .002) as well as with SBP; (b) or with the number of moderate METs (b-coefficient = -0.192, P = .025) as well as with age and SBP. No significant associations were observed between the intensity of physical exercise and arterial stiffness in the overweight-obese group. Physical activity is negatively associated with arterial stiffness in postmenopausal women with normal weight. This association was not observed in overweight or obese women.