Despite decades of unequivocal evidence that waist circumference provides both independent and additive information to BMI for predicting morbidity and risk of death, this measurement is not routinely obtained in clinical practice. This Consensus Statement proposes that measurements of waist circumference afford practitioners with an important opportunity to improve the management and health of patients. We argue that BMI alone is not sufficient to properly assess or manage the cardiometabolic risk associated with increased adiposity in adults and provide a thorough review of the evidence that will empower health practitioners and professional societies to routinely include waist circumference in the evaluation and management of patients with overweight or obesity. We recommend that decreases in waist circumference are a critically important treatment target for reducing adverse health risks for both men and women. Moreover, we describe evidence that clinically relevant reductions in waist circumference can be achieved by routine, moderate-intensity exercise and/or dietary interventions. We identify gaps in the knowledge, including the refinement of waist circumference threshold values for a given BMI category , to optimize obesity risk stratification across age, sex and ethnicity. We recommend that health professionals are trained to properly perform this simple measurement and consider it as an important 'vital sign' in clinical practice.

Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic morbidity and mortality. Emerging evidence also suggests that ectopic fat deposition, including hepatic and epicardial fat, might contribute to increased atherosclerosis and cardiometabolic risk. This joint position statement from the International Atherosclerosis Society and the International Chair on Cardiometabolic Risk Working Group on Visceral Obesity summarises the evidence for visceral adiposity and ectopic fat as emerging risk factors for type 2 diabetes, atherosclerosis, and cardiovascular disease, with a focus on practical recommendations for health professionals and future directions for research and clinical practice. We discuss the measurement of visceral and ectopic fat, pathophysiology and contribution to adverse health outcomes, response to treatment, and lessons from a public health programme targeting visceral and ectopic fat. We identify knowledge gaps and note the need to develop simple, clinically applicable tools to be able to monitor changes in visceral and ectopic fat over time. Finally, we recognise the need for public health messaging to focus on visceral and ectopic fat in addition to excess bodyweight to better combat the growing epidemic of obesity worldwide. Measurement of visceral and ectopic fatThe development of medical imaging has been a remarkable advance that has revolutionised the study of human body composition, including visceral fat. [18][19][20] Cross-sectional

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This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis.

Objectives To evaluate (1) the inter-individual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) levels achieved with statin therapy, (2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy, and (3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and CVD risk. Background Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease (CVD) risk is not well documented. Methods Meta-analysis of individual patient data from 8 randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Results Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large inter-individual variability in the reductions of LDL-C, non-HDL-C and apoB achieved with a fixed statin dose. Over 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target below 70 mg/dL. Compared to patients who achieved an LDL-C > 175 mg/dL, those who reached an LDL-C 75-100 mg/dL, 50-75 mg/dL and < 50 mg/dL had adjusted hazard ratios for major cardiovascular events of 0.56 (95%CI 0.46-0.67), 0.51 (95%CI 0.42-0,62) and 0.44 (95%CI 0.35-0.55), respectively. Similar associations were observed for non-HDL-C and apoB. Conclusions The reduction of LDL-C, non-HDL-C and apoB levels achieved with statin therapy displays large inter-individual variation. Among trial participants treated with high-dose statin therapy, over 40% do not reach an LDL-C target <70 mg/dL. Patients who achieve very low LDL-C levels have a lower risk of major cardiovascular events than those achieving moderately low levels.

Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800).

High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM. Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials.

The main process that triggers pathological mineralization of the aortic valve remains elusive. 3 Recently, 3 successive studies with a Mendelian randomization design have reported a significant association between the LPA gene variant (rs10455872), which genetically determines the lipoprotein(a) [Lp(a)] plasma level, and CAVD. [4][5][6] These studies thus suggested a causal relationship between Lp(a) and CAVD risk. Lp(a) is a low-density lipoprotein (LDL)-like particle in which an apolipoprotein(a) is linked by a disulfide bridge to apolipoprotein B. Lp(a) is a major carrier of oxidized phospholipids (OxPLs) and has been associated Background-Mendelian randomization studies have highlighted that lipoprotein(a) [Lp(a)] was associated with calcific aortic valve disease (CAVD). Lp(a) transports oxidized phospholipids with a high content in lysophosphatidylcholine. Autotaxin (ATX) transforms lysophosphatidylcholine into lysophosphatidic acid. We hypothesized that ATXlysophosphatidic acid could promote inflammation/mineralization of the aortic valve. Methods and Results-We have documented the expression of ATX in control and mineralized aortic valves. By using different approaches, we have also investigated the role of ATX-lysophosphatidic acid in the mineralization of isolated valve interstitial cells and in a mouse model of CAVD. Enzyme-specific ATX activity was elevated by 60% in mineralized aortic valves in comparison with control valves. Immunohistochemistry studies showed a high level of ATX in mineralized aortic valves, which colocalized with oxidized phospholipids and apolipoprotein(a). We detected a high level of ATX activity in the Lp(a) fraction in circulation. Interaction between ATX and Lp(a) was confirmed by in situ proximity ligation assay. Moreover, we documented that valve interstitial cells also expressed ATX in CAVD. We showed that ATX-lysophosphatidic acid promotes the mineralization of the aortic valve through a nuclear factor κB/interleukin 6/bone morphogenetic protein pathway. In LDLR -/-/ApoB 100/100 /IGFII mice, ATX is overexpressed and lysophosphatidic acid promotes a strong deposition of hydroxyapatite of calcium in aortic valve leaflets and accelerates the development of CAVD. Conclusions-ATX