Japan Atherosclerosis Society

To measure the stiffness of the aorta, femoral artery and tibial artery noninvasively, cardio-ankle vascular index (CAVI) which is independent of blood pressure was developed. The formula for measuring this index is; CAVI=a{(2rho/DeltaP) x ln(Ps/Pd)PWV(2)} + b where, Ps and Pd are systolic and diastolic blood pressures respectively, PWV is pulse wave velocity between the heart and ankle, DeltaP is Ps - Pd, rho is blood density, and a and b are constants. This equation was derived from Bramwell-Hill's equation(1)), and stiffness parameter(2)). To elucidate the clinical utility of CAVI, the reproducibility and dependence on blood pressure were studied using VaSera (Fukuda Denshi Co., Ltd.). Furthermore, CAVI in hemodialysis patients with or without atherosclerotic diseases was measured. The average coefficient of variation for five measurements among 22 persons was 3.8%. In hemodialysis patients (n = 482), CAVI was correlated weakly with systolic and diastolic blood pressures (R = 0.175, 0.006), while brachial-ankle PWV was correlated strongly with systolic and diastolic blood pressures (R = 0.463, 0.335). CAVI in hemodialysis patients without signs of atherosclerotic diseases (NA) was 8.1 +/- 0.3 (mean +/- SD). That in patients receiving percutaneous transluminal coronary angioplasty was 8.8 +/- 0.3 (p < 0.05 vs. NA). CAVI in patients with ischemic change in their electrocardiogram (ECG) was 8.5 +/- 0.3 (p < 0.05 vs. NA). That in patients with diabetes mellitus was 8.5 +/- 0.3 (p < 0.002 vs. NA). CAVI in the patients with all three complications was 8.9 +/- 0.35 (p < 0.001 vs. NA). These results suggested that CAVI could reflect arteriosclerosis of the aorta, femoral artery and tibial artery quantitatively.

The constellation of metabolic abnormalities including centrally distributed obesity, decreased high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, elevated blood pressure (BP), and hyperglycaemia is known as the metabolic syndrome. Associated with a 3 fold and 2 fold increase in type 2 diabetes and cardiovascular disease (CVD), respectively, it is thought to be a driver of the modern day epidemics of diabetes and CVD and has become a major public health challenge around the world. Since its initial description, several definitions of the syndrome have emerged. Each of these definitions used differing sets of criteria, which reflected contrasting views on pathogenic mechanisms and the need for clinical usefulness. The use of these definitions to conduct research into the metabolic syndrome in diverse populations resulted in wide ranging prevalence rates, inconsistencies and confusion, and spurred on the vigorous debate regarding how the metabolic syndrome should be defined. In response to this controversy, the International Diabetes Federation (IDF) has recently proposed a new definition, which is applicable to populations around the world. It is envisaged that the development of the new definition for the metabolic syndrome will help resolve the confusion caused by the number of earlier attempts to define this important entity.

Chapter 1. Summary of the Guidelines… …………………………………………………………………………………… Chapter 2. Clinical Diagnosis of Atherosclerosis… ……………………………………………………………………… Chapter 3. Comprehensive Risk Assessment… …………………………………………………………………………… 3-1.Risk Factor Assessment… …………………………………………………………………………………………… 3-2.Disease Concept and Diagnostic Criteria for Metabolic Syndrome… ………………………………………… Chapter 4. Comprehensive Risk Management… ………………………………………………………………………… 4-1.Absolute Risk of Atherosclerotic Cardiovascular Diseases (ASCVD) and Lipid-Management Targets…… 4-2.…LifestyleModification… ……………………………………………………………………………………………… 4-3.Drug Therapy… ……………………………………………………………………………………………………… 4-4.Managing Major High-Risk Conditions…………………………………………………………………………… 4-5.Implementation of Comprehensive Risk Assessment and Management… …………………………………… Chapter 5. Familial Hypercholesterolemia… ……………………………………………………………………………… Chapter 6.Other Types of Primary Dyslipidemias… …………………………………………………………………… Chapter 7. Elderly… ………………………………………………………………………………………………………… Chapter 8. Women… ………………………………………………………………………………………………………… Chapter 9. Children… …………………………………………………………………………………………………………

Accumulating clinical evidence has suggested serum triglyceride (TG) is a leading predictor of atherosclerotic cardiovascular disease, comparable to low-density lipoprotein (LDL)-cholesterol (C) in populations with type 2 diabetes, which exceeds the predictive power of hemoglobinA1c. Atherogenic dyslipidemia in diabetes consists of elevated serum concentrations of TG-rich lipoproteins (TRLs), a high prevalence of small dense low-density lipoprotein (LDL), and low concentrations of cholesterol-rich high-density lipoprotein (HDL)2-C. A central lipoprotein abnormality is an increase in large TG-rich very-low-density lipoprotein (VLDL)1, and other lipoprotein abnormalities are metabolically linked to increased TRLs. Insulin critically regulates serum VLDL concentrations by suppressing hepatic VLDL production and stimulating VLDL removal by activation of lipoprotein lipase. It is still debated whether hyperinsulinemia compensatory for insulin resistance is causally associated with the overproduction of VLDL. This review introduces experimental and clinical observations revealing that insulin resistance, but not hyperinsulinemia stimulates hepatic VLDL production. LDL and HDL consist of heterogeneous particles with different size and density. Cholesterol-depleted small dense LDL and cholesterol-rich HDL2 subspecies are particularly affected by insulin resistance and can be named "Metabolic LDL and HDL," respectively. We established the direct assays for quantifying small dense LDL-C and small dense HDL(HDL3)-C, respectively. Subtracting HDL3-C from HDL-C gives HDL2-C. I will explain clinical relevance of measurements of LDL and HDL subspecies determined by our assays. Diabetic kidney disease (DKD) substantially worsens plasma lipid profile thereby potentiated atherogenic risk. Finally, I briefly overview pathophysiology of dyslipidemia associated with DKD, which has not been so much taken up by other review articles.

Intestinal flora (microbiota) have recently attracted attention among lipid and carbohydrate metabolism researchers. Microbiota metabolize resistant starches and dietary fibers through fermentation and decomposition, and provide short chain fatty acids (SCFAs) to the host. The major SCFAs acetates, propionate and butyrate, have different production ratios and physiological activities. Several receptors for SCFAs have been identified as the G-protein coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3), GPR43/FFAR2, GPR109A, and olfactory receptor 78, which are present in intestinal epithelial cells, immune cells, and adipocytes, despite their expression levels differing between tissues and cell types. Many studies have indicated that SCFAs exhibit a wide range of functions from immune regulation to metabolism in a variety of tissues and organs, and therefore have both a direct and indirect influence on our bodies. This review will focus on SCFAs, especially butyrate, and their effects on various inflammatory mechanisms including atherosclerosis. In the future, SCFAs may provide new insights into understanding the pathophysiology of chronic inflammation, metabolic disorders, and atherosclerosis, and we can expect the development of novel therapeutic strategies for these diseases.

Diabetic macroangiopathy, atherosclerosis secondary to diabetes mellitus (DM), causes cerebro-cardiovascular diseases, which are major causes of death in patients with DM and significantly reduce their quality of life. The alterations in vascular homeostasis due to endothelial and vascular smooth muscle cell dysfunction are the main features of diabetic macroangiopathy. Although multiple metabolic abnormalities that characterize diabetes are involved in the progression of atherosclerosis in patients with DM, it may be said that prolonged exposure to hyperglycemia and insulin resistance clustering with other risk factors such as obesity, arterial hypertension, and dyslipidemia play crucial roles. Laboratory and clinical researches in the past decades have revealed that major biochemical pathways involved in the development of diabetic macroangiopathy are as follows: overproduction of reactive oxygen species, increased formation of advanced glycation end-products (AGEs) and activation of the AGEs-receptor for AGE axis, polyol and hexosamine flux, protein kinase C activation, and chronic vascular inflammation. Among them, oxidative stress is considered to be a key factor.

Metabolic syndrome is associated with dysfunctional adipose tissue that is most likely a consequence of the enlargement of adipocytes and infiltration of macrophages into adipose tissue. Obesity and ectopic lipid deposition are major risk factors for diseases ranging from insulin resistance to type 2 diabetes and atherosclerosis. Enlargement of adipocytes, due to impaired adipocyte differentiation, leads to a chronic state of inflammation in the adipocytes and adipose tissue with a reduction in the secretion of adiponectin and increase in the secretion of proinflammatory cytokines such as interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1. The secretion of cytokines like tumour necrosis factor (TNF)- alpha, mainly from macrophages, enhances local inflammation. These proinflammatory cytokines might also substantially affect cardiovascular function and morphology. Furthermore, a proinflammatory state in adipose tissue can lead to local insulin resistance with an impaired inhibitory effect of insulin on the release of FFAs and endothelial dysfunction that clearly promotes cardiovascular diseases and type 2 diabetes. The underlying mechanisms of ectopic fat accumulation in various tissues and the impact on metabolic syndrome and its association with insulin resistance are discussed.

Among the various atherosclerotic cardiovascular diseases (CVDs), these guidelines primarily deal with cerebrovascular disease, peripheral arterial disease (PAD) and coronary artery disease (CAD), which occur in association with atherosclerosis and is closely related to dyslipidemia.

The cardio-ankle vascular index (CAVI) is a new index of the overall stiffness of the artery from the origin of the aorta to the ankle. The most conspicuous feature of CAVI is its independence of blood pressure at the time of measurement.CAVI increases with age and in many arteriosclerotic diseases, such as coronary artery disease, carotid arteriosclerosis, chronic kidney disease and cerebrovascular disease, and is related to many coronary risk factors, such as hypertension, diabetes mellitus, dyslipidemia and smoking. Furthermore, CAVI decreases by controlling diabetes mellitus and hypertension, and also by abstaining from smoking. This suggests that CAVI is a physiological surrogate marker of athero- or arteriosclerosis, and also might be an indicator of lifestyle modification.Recently, it has been reported that CAVI and several left ventricular functions are co-related, suggesting a connection between the heart muscle and vascular function.This review covers the principles of CAVI and our current knowledge about CAVI, focusing on its roles and future outlook.

Although abdominal obesity or visceral obesity is considered to be one of the components of metabolic syndrome and to have an important role in a cluster of cardiovascular risks, there is no consensus about the definition and diagnostic criteria for this syndrome, probably because there is considerable disagreement about the location and definition of abdominal obesity or visceral obesity.In this review article, the important role of visceral fat accumulation in the development of a variety of lifestyle-related diseases is shown, including cardiovascular disease based on our clinical studies using CT scans, and the mechanism of these disorders is discussed, focusing on adipocytokines, especially adiponectin.The importance of diagnosing metabolic syndrome, in which visceral fat accumulation plays an essential role in the development of multiple risk factors, should be emphasized because lifestyle modification for the reduction of visceral fat may be very effective for the reduction of risks of this type, namely metabolic syndrome in the narrow sense.

Although the mortality rate from cardiovascular disease (CVD) in Japan remains lower than that in Western countries, the need for the prevention of atherosclerotic diseases still merits emphasis. Cardiovascular disease develops due to the accumulation of risk factors such as visceral obesity, impaired glucose tolerance and diabetes, dyslipidemia, metabolic dysfunction associated with steatotic liver disease, hypertension, and chronic kidney disease. Dietary therapy must comprehensively improve these factors through the intake of nutrients and food components. This narrative review aims to confirm the effects of well-known nutrients that influence atherosclerotic risk factors and foods providing each nutrient in the Japanese diet. Furthermore, the actual dietary intake of the Japanese population is described. Target foods and dietary habits to modify patients' diets should be determined through nutrition assessment. Reducing carbohydrate intake requires limiting confectioneries, sweet beverages, and sweet fruits while avoiding the consumption of a lot of refined grains at once. The consumption of foods rich in saturated fatty acids, such as lard, beef tallow, butter, fatty red meat, fresh cream, and trans fatty acids contained in shortening, margarine, oily processed and fried foods, should be reduced. To meet the dietary fiber intake requirement, more unpolished grains, vegetables, citrus or whole fruits, seaweed, mushrooms, and konjac should be consumed. Fish intake is higher in Japan than in Western countries but it has been decreasing in younger generations, indicating the need for education and environments that encourage fish consumption for EPA and DHA intake and limit excess oil intake. Japanese people have higher candidate gene polymorphisms responsible for salt-sensitive hypertension than Caucasians; therefore, strict salt reduction is desirable. Sodium is included in salt, seasonings, and sodium salt additives in take-away, prepared, and ultra-processed foods, the cumulative impact of which cannot be ignored. The Japan Atherosclerosis Society (JAS) recommends a dietary pattern called "The Japan Diet," featuring higher consumption of fish, soybeans and soy products, vegetables, citrus fruits, low-fat milk and dairy products, seaweed/mushrooms/konjak, and unrefined cereals with reduced consumption of animal fat, fatty meat and poultry, sweets including desserts and snacks, and alcoholic drinks, along with reduced salt intake. "The Japan Diet", a reasonable and useful strategy for nutrition therapy, improves multiple atherosclerotic risk factors comprehensively by providing prescribed nutrients. Nutrition education for "The Japan Diet" intake improved serum lipid and metabolic parameters in patients with dyslipidemia. However, clinical intervention studies on patients with atherosclerotic risk factors remain limited. Further studies on the effect of "The Japan Diet" on CVD prevention are needed.

Cardiovascular disease remains a leading cause of morbidity and mortality in East Asia, although its epidemiological profile differs substantially from that of Western populations. As East Asia experiences rapid increases in chronic kidney disease, diabetes, multimorbidity, and heart failure driven by population aging, accurate cardiovascular risk prediction has become increasingly important for the risk-stratified prevention of these diseases. Traditional risk prediction models, including the Framingham Risk Score, Pooled Cohort Equations, and SCORE, were derived largely from Western populations and often overestimated the risk in East Asian cohorts without recalibration. In 2025, the American Heart Association introduced the PREVENT equations to estimate 10-year and 30-year risks of total cardiovascular disease, atherosclerotic cardiovascular disease, and heart failure within an integrated cardiovascular-kidney-metabolic framework. Given the growing globalization of cardiovascular prevention and international clinical research, understanding whether PREVENT performs well in East Asian populations has important implications for the clinical implementation and harmonization of risk assessment frameworks. This review summarizes the evolution of cardiovascular risk prediction, key innovations of PREVENT, and emerging validation evidence from East Asia. Early studies from Korea and China suggest the reasonable transportability of these approaches. However, evidence from Japan remains limited, and further validation and recalibration are warranted. We also discuss the challenges related to heart failure prediction, add-on variables, electronic health record data infrastructure, and AI-assisted risk assessment.

Polyunsaturated fatty acids (PUFAs) are essential fatty acids that cannot be synthesized endogenously and must therefore be obtained through dietary intake.PUFAs are broadly classified into omega-3 PUFAs, represented by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFAs, represented by arachidonic acid (AA) and dihomo-γ-linolenic acid (DGLA).The relationship between PUFAs and atrial fibrillation (AF) has attracted considerable attention for many years.Previous studies have suggested that omega-3 PUFAs may exert antiarrhythmic effects and reduce the risk of AF 1) .Several mechanisms have been proposed to explain the anti-arrhythmic effects of omega-3 PUFAs.Experimental studies suggest that EPA and DHA may suppress AF by modifying the ionic channels in the atrial cell membrane and stabilizing atrial electrophysiology through inhibition of pulmonary vein ectopy and early afterdepolarizations, attenuating inflammatory signaling pathways, reducing atrial structural remodeling through modulation of connexins, matrix metalloproteinases, and collagen expression, and influencing autonomic regulation 2,3) .Collectively, these effects may contribute to the prevention of atrial fibrosis and remodeling, and the maintenance of atrial electrical stability.However, growing evidence in recent years has raised concerns regarding a potential association between omega-3 PUFAs and an increased risk of AF.Several large randomized controlled trials evaluating high-dose omega-3 PUFA supplementation have attracted particular attention.In the STRENGTH trial (patients with various cardiovascular disease risks; EPA+DHA, 4 g/day), the REDUCE-IT trial (patients with various cardiovascular disease risks; EPA, 4 g/

Atrial fibrillation is one of the most important causes of ischemic stroke and it is strongly associated with recurrent stroke, systemic embolism, heart failure, cognitive decline, and mortality. Oral anticoagulation, preferably direct oral anticoagulants, remains the cornerstone of secondary stroke prevention in patients with atrial fibrillation and a history of ischemic stroke. However, ischemic stroke may still occur despite appropriate anticoagulation therapy, a condition often referred to as breakthrough ischemic stroke. This residual risk reflects heterogeneous mechanisms, including inadequate anticoagulant exposure, atrial cardiomyopathy, left atrial appendage thrombus, large-artery atherosclerosis, small-vessel disease, cancer-associated thrombosis, and other competing etiologies. Rhythm control has re-emerged as a disease-modifying strategy after the EAST-AFNET 4 trial, and its prespecified subgroup analysis suggested a potential benefit in patients with prior stroke. However, the recently reported STABLED randomized clinical trial, which specifically evaluated catheter ablation in addition to edoxaban-based standard therapy after a recent ischemic stroke, did not demonstrate a significant reduction in recurrent ischemic stroke, systemic embolism, all-cause mortality, or hospitalization for heart failure. These findings do not negate the value of rhythm control for symptom relief, atrial fibrillation burden reduction, and selected cardiovascular outcomes; however, they challenge the assumption that the restoration of sinus rhythm alone is sufficient for secondary stroke prevention. Future strategies should integrate optimized anticoagulation and early rhythm control when appropriate, with a systematic evaluation of competing stroke mechanisms, vascular risk factor control, and selected left atrial appendage interventions. The next frontier is not rhythm control alone but rhythm control embedded within mechanism-based secondary stroke prevention.

AIM: Familial chylomicronemia syndrome (FCS) is a rare disorder characterized by the accumulation of chylomicrons in the circulation due to genetic defects or autoantibodies affecting lipoprotein lipase (LPL), the key enzyme responsible for the metabolism of chylomicrons and very-low-density lipoproteins (VLDL), or its associated proteins, including apolipoprotein (apo) C-II, apoA-V, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and lipase maturation factor 1 (LMF1). This condition is associated with markedly elevated serum triglyceride (TG) levels and, in severe cases, recurrent episodes of pancreatitis and eruptive xanthomas. Among these etiologies, genetic deficiency of GPIHBP1 is exceedingly rare. We aimed to clarify the clinical and genetic basis and treatment strategies of a patient with GPIHBP1 deficiency. METHODS: A 47-year-old woman with a childhood diagnosis of FCS presented with severe epigastric pain and was admitted to Rinku General Medical Center for emergency management of acute pancreatitis secondary to severe chylomicronemia. She had a history of severe hypertriglyceridemia complicated by pancreatitis during her first pregnancy and extreme hypertriglyceridemia exceeding 6,000 mg/dL during her second pregnancy without the development of pancreatitis. DNA sequence analysis was performed as a clinical diagnostic test and outsourced to KUBIX Inc. (Hakusan, Ishikawa, Japan). RESULTS: Laboratory evaluation revealed marked hypertriglyceridemia (1,262 mg/dL) with a type V hyperlipoproteinemia pattern. Serum preheparin LPL mass was markedly reduced, and circulating GPIHBP1 was undetectable. Genetic analysis identified a novel homozygous frameshift mutation in the GPIHBP1 gene (NM_178172.4:c.20del [p.Val7AlafsTer73]), which has not been previously reported in public databases. No pathogenic variants were detected in other LPL-related genes. Acute pancreatitis improved rapidly with fasting and intravenous fluid therapy. Strict dietary fat restriction, followed by the addition of the selective PPARα modulator pemafibrate, successfully maintained TG levels below 500 mg/dL during follow-up. CONCLUSION: We report an extremely rare case of FCS caused by a novel homozygous mutation in the GPIHBP1 gene, in which pregnancy served as a major trigger for severe hypertriglyceridemia. Early diagnosis and strict lipid control are essential to prevent recurrent pancreatitis in patients with GPIHBP1 deficiency.

AIM: To investigate the effects of temperature exposure on the incidence of cardiovascular and cerebrovascular diseases in Zhanjiang, a subtropical coastal city in China. METHODS: We analyzed hospitalization data from 2009 to 2023 using generalized additive models (GAMs) and distributed lag nonlinear models (DLNMs) to examine the exposure-response relationships and lagged effects of daily maximum temperature on stroke (CVA), acute coronary syndrome (ACS), and acute aortic syndrome (AAS). RESULTS: Distinct temperature-associated risk patterns were observed for each disease type. ACS showed the strongest association, with significant risk increases at 1-day (relative risk [RR] = 1.19) and 5-day lags (RR = 1.12). The risk of CVA was moderately elevated at lower temperatures (22.7℃; RR = 1.08), whereas AAS exhibited a delayed peak at 5 days (RR = 1.29). CONCLUSIONS: These subtropical patterns differ from those reported in temperate regions. Our findings support climate-specific warnings: namely, multi-day monitoring for CVA at lower temperatures, immediate and sustained alerts for ACS, and focused surveillance approximately 5 days after exposure for AAS.