Lifestyle factors and high-risk atherosclerosis: Pathways and mechanisms beyond traditional risk factors

Despite major efforts to reduce atherosclerotic cardiovascular disease (ASCVD) burden with conventional risk factor control, significant residual risk remains. Recent evidence on non-traditional determinants of cardiometabolic health has advanced our understanding of lifestyle-disease interactions. Chronic exposure to environmental stressors like poor diet quality, sedentarism, ambient air pollution and noise, sleep deprivation and psychosocial stress affect numerous traditional and non-traditional intermediary pathways related to ASCVD. These include body composition, cardiorespiratory fitness, muscle strength and functionality and the intestinal microbiome, which are increasingly recognized as major determinants of cardiovascular health. Evidence points to partially overlapping mechanisms, including effects on inflammatory and nutrient sensing pathways, endocrine signalling, autonomic function and autophagy. Of particular relevance is the potential of low-risk lifestyle factors to impact on plaque vulnerability through altered adipose tissue and skeletal muscle phenotype and secretome. Collectively, low-risk lifestyle factors cause a set of phenotypic adaptations shifting tissue cross-talk from a proinflammatory milieu conducive for high-risk atherosclerosis to an anti-atherogenic milieu. The ketone body ß-hydroxybutyrate, through inhibition of the NLRP-3 inflammasome, is likely to be an intermediary for many of these observed benefits. Adhering to low-risk lifestyle factors adds to the prognostic value of optimal risk factor management, and benefit occurs even when the impact on conventional risk markers is discouragingly minimal or not present. The aims of this review are (a) to discuss novel lifestyle risk factors and their underlying biochemical principles and (b) to provide new perspectives on potentially more feasible recommendations to improve long-term adherence to low-risk lifestyle factors

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD

Three-Dimensional Echocardiography: Rational Mode of Component Images for Left Ventricular Volume Quantitation

Three-dimensional echocardiography (3DE) improves the accuracy of left ventricle (LV) volumetry compared with the two-dimensional echocardiography (2DE) approach because geometric assumptions in the algorithms may be eliminated. The relationship between accuracy of mode (short- versus long-axis planimetry) and the number of component images versus time required for analysis remains to be determined. Sixteen latex models simulating heterogeneously distorted (aneurysmatic) human LVs (56–303 ml; mean 182 8 82 ml) were scanned from an ‘apical’ position (simultaneous 2DE and 3DE). For 3DE volumetry, the slice thickness was varied for the short (C-scan) and long axes (B-scan) in 5-mm steps between 1 and 25 mm. The mean differences (trueechocardiographic volumes) were 16.5 8 44.3 ml in the 2DE approach (95% confi dence intervals –27.8 to +60.8) and 0.6 8 4.0 ml (short axis; 95% confi dence intervals –3.4 to +4.6) as well as 2.1 8 9.9 ml (long axis; 95% confi dence intervals –7.8 to +12.0) in the 3DE approach (in both cases, the slice thickness was 1 mm). Above a slice thickness of 15 mm, the 95% confi dence intervals increased steeply; in the short versus long axes, these were –6.5 to +8.5 versus –7.0 to +10.6 at 15 mm and –10.1 to +15.7 versus –11.3 to +10.9 at 20 mm. The intra-observer variance differed signifi cantly (p ! 0.001) only above 15 mm (short axis). Time required for analysis derived by measuring short-axis slice thicknesses of 1, 15, and 25 mm was 58 8 16, 7 8 2 and 3 8 1 min, respectively. The most rational component image analysis for 3DE volumetry in the in vitro model uses short-axis slices with a thickness of 15 mm

Chronic Development of Ischaemic Mitral Regurgitation during Post-Infarction Remodelling

Background/Aims: Mitral regurgitation (MR) following myocardial infarction (MI) may be a (sub)acute complication which independently predicts reduced survival. We sought to evaluate the chronic development of MR as potential consequence of left-ventricular (LV) remodelling, the latter being a long-term process. Methods and Results: Retrospectively, 103 post-MI patients were included according to a standardised Doppler echocardiogram ! 3 months following MI (20 8 25 days post-MI) and a follow-up examination 1 6 months after the first examination (5.1 8 3.1 years post- MI). Patients were clinically followed up for 7.6 8 2.7 years. Group I patients were defined as those showing new development or deterioration in one of three grades of MR, and group II those without this criterion (MR grade acute 0.17 vs. 0.27, p = 0.7, and chronic 1.53 vs. 0.19, p ! 0.0001). Patient characteristics were similar in respect of age, gender, size and location of infarction. However, group I patients had coronary artery disease with more vessels involved. With regard to echocardiographic parameters of significantly enlarged LV chamber size in group I vs. group II, the significant decrease in LV performance was more pronounced and occurred concomitant with a higher degree of symptomatic congestive heart failure and greater need for heart failure medications in group I. Mortality in group I patients was 39 versus 9% in group II patients (p = 0.0002), approximating an odds ratio of 6.4697 (95% confidence interval: 2.211– 18.931). Conclusion: First of all, this retrospective study indicates that MR may be detected in patients after MI during a long-term follow-up most probably due to geometric distortions of LV remodelling resulting in a significantly higher mortality. Since this process is known to become irreversible at a certain point, serial echocardiography may help to detect MR in post-MI patients and thus pave the way for appropriate treatment

Head-to-Head Comparison of Dobutamine Stress Echocardiography and Cardiac Computed Tomography for the Detection of Significant Coronary Artery Disease

Objectives: Dobutamine stress echocardiography (DSE) and contrast-enhanced electron beam tomography (EBCT) both have the potential to noninvasively detect coronary artery disease (CAD). We compared the accuracy of both methods to detect significant CAD in a direct comparison. Methods: 79 patients (32 women, 47 men, mean age 62 years) who were admitted for coronary angiography due to suspected CAD were studied. By EBCT coronary calcification (CAC) as well as angiography (CTA) was assessed. Presence of significant CAD was assumed if the calcium score exceeded 400 or the contrast-enhanced images displayed significant lumen reduction. DSE was performed using a standard protocol (5–40 _g/kg/min dobutamine plus 0.25–1.0 mg atropine if necessary). DSE and EBCT were independently evaluated concerning the presence of signficant CAD. Results were compared to invasive, quantitative coronary angiography. Results: 6 patients (8%) in DSE and 2 patients (3%) in EBCT were unevaluable for various reasons and therefore excluded from further analysis. In the remaining 71 patients, 33 pa- tients (46%) showed significant CAD. DSE demonstrated a sensitivity of 70% (23/33) and a specificity of 84% (32/38). EBCT showed a sensitivity of 91% (30/33) and a specificity of 74% (28/38). By combining DSE and EBCT sensitivity increased to 97% with a specificity of 63%. Conclusions: In a blinded comparison, DSE demonstrated lower sensitivity but higher specificity than EBCT for the detection of significant CAD. Sensitivity was improved by comb ining both modalities

High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation

Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD

Tissue Doppler vs Strain Rate Imaging for detecting regional myocardial ischemia during dobutamine stress echocardiography

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Comparison of deformation imaging and velocity imaging for detecting regional inducible ischaemia during dobutamine stress echocardiography

Aims To determine whether Doppler based myocardial tissue velocity imaging (TVI) or strain rate imaging (SRI) is more accurate in detecting stress-induced ischaemia during dobutamine stress echocardiography (DSE).status: publishe

Strain-rate imaging during dobutamine stress echocardiography provides objective evidence of inducible ischemia

BACKGROUND: Interpretation of dobutamine stress echocardiography (DSE) is subjective and strongly dependent on the skills of the reader. Strain-rate imaging (SRI) by tissue Doppler may objectively analyze regional myocardial function. This study investigated SRI markers of stress-induced ischemia and analyzed their applicability in a clinical setting. METHODS AND RESULTS: DSE was performed in 44 patients with known or suspected coronary artery disease. Simultaneous perfusion scintigraphy served as a "gold standard" to define regional ischemia. All patients underwent coronary angiography. Segmental strain and strain rate were analyzed at all stress levels by measuring amplitude and timing of deformation and visual curved M-mode analysis. Results were compared with conventional stress echo reading. In nonischemic segments, peak systolic strain rate increased significantly with dobutamine stress (-1.6+/-0.6 s-1 versus -3.4+/-1.4 s-1, P<0.01), whereas strain during ejection time changed only minimally (-17+/-6% versus -16+/-9%, P<0.05). During DSE, 47 myocardial segments in 19 patients developed scintigraphy-proven ischemia. Strain-rate increase (-1.6+/-0.8 s-1 versus -2.0+/-1.1 s-1, P<0.05) and strain (-16+/-7% versus -10+/-8%, P<0.05) were significantly reduced (both P<0.01 compared with nonischemic). Postsystolic shortening (PSS) was found in all ischemic segments. The ratio of PSS to maximal segmental deformation was the best quantitative parameter to identify stress-induced ischemia. Compared with conventional readings, SRI curved M-mode assessment improved sensitivity/specificity from 81%/82% to 86%/90%. CONCLUSIONS: During DSE, SRI quantitatively and qualitatively differentiates ischemic and nonischemic regional myocardial response to dobutamine stress. The ratio of PSS to maximal strain may be used as an objective marker of ischemia during DSE.status: publishe