Aim: Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor (PPAR)-α, a key regulator of lipid and glucose metabolism. We compared the efficacy and safety of pemafibrate with those of bezafibrate, a nonselective PPAR-α agonist.

Methods: In this randomized crossover study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks. The primary endpoint was percent change (%Change) from baseline in TG levels, while the secondary endpoints were %Change in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I) levels.

Results: The %Change in TG and Apo A-I levels was significantly greater with pemafibrate than with bezafibrate (−46.1% vs. −34.7%, p＜0.001; 9.2% vs. 5.7%, p =0.018, respectively). %Change in HDL-C levels was not significantly different between the two treatments. %Change in liver enzyme levels was markedly decreased with pemafibrate than with bezafibrate. Creatinine levels significantly increased in both treatments; however, its %Change was significantly lower with pemafibrate than with bezafibrate (5.72% vs. 15.5%, p＜0.001). The incidence of adverse events (AEs) or serious AEs did not differ between the two treatments; however, the number of patients with elevated creatinine levels (≥ 0.5 mg/dL and/or 25% from baseline) was significantly lower in the bezafibrate group than in the pemafibrate group (16/60 vs. 3/60, p =0.004).

Conclusion: Compared with bezafibrate, pemafibrate is more effective in decreasing TG levels and increasing Apo A-I levels and is safer regarding liver and renal function.

Aims: The associations between low-density lipoprotein cholesterol (LDL-C) and the risk of cardiovascular disease (CVD) subtypes are not well established among the Japanese population. This study used longitudinal data from the Aichi Workers’ Cohort Study to explore the association between LDL-C levels and the risk of coronary heart disease (CHD) and stroke subtypes.

Methods: Pooled data of 8966 adults (7093men and 1903 women) who were recruited between (2002) and (2008) were used for the current analysis. Propensity scores for the LDL-C categories were generated using multinomial logistic regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from the inverse probability weighted Cox proportional hazards model for LDL-C category associations with risks of CHD, stroke subtypes, and CVD.

Results: During a median follow-up of 12 years, 122 strokes (57 ischemic strokes, 25 intracerebral hemorrhage, and 40 unknown subtypes) and 82 cases of CHD were observed. LDL-C 160– mg/dL compared to LDL-C 100–119 mg/dL was positively and significantly associated with the risk of CHD (HR: 4.56; 95% CI: 1.91–10.9) but not with ischemic stroke (HR: 0.99; 95% CI: 0.44–2.22). LDL-C was inversely associated with the risk of intracerebral hemorrhage (P for trend=0.009).

Conclusion: In middle-aged Japanese workers, LDL-C was significantly and positively associated with CHD, but not with ischemic stroke. LDL-C was inversely significantly associated with intracerebral hemorrhage.

Aims: Genetic and medical insights from studies on cardioprotective phenotypes aid the development of novel therapeutics. This study identified genetic variants associated with supernormal coronary arteries using genome-wide association study data and the corresponding genes based on expression quantitative trait loci (eQTL).

Methods: Study participants were selected from two Korean cohorts according to inclusion criteria that included males with high cardiovascular risk (Framingham risk score ≥ 14, 10-year risk ≥ 16%) but with normal coronary arteries (supernormal group) or coronary artery disease (control group). After screening 12,309 individuals, males meeting the supernormal phenotype (n=72) and age-matched controls (n=94) were enrolled. Genetic variants associated with the supernormal phenotype were identified using Firth’s logistic regression, and eQTL was used to evaluate whether the identified variants influence the expression of particular genes in human tissues.

Results: Approximately 5 million autosomal variants were tested for association with the supernormal phenotype, and 10 independent loci suggestive of supernormal coronary arteries (p＜5.0×10⁻⁵) were identified. The lead variants were seven intergenic single-nucleotide polymorphisms (SNPs), including one near PBX1, and three intronic SNPs, including one in PPFIA4. Of these variants or their proxies, rs9630089, rs6427989, and rs4984694 were associated with expression levels of SLIT1 and ARHGAP19, PPFIA4, and METTL26 in human tissues, respectively. These eQTL results supported their potential biological relevance.

Conclusions: This study identified genetic variants and eQTL genes associated with supernormal coronary arteries. These results suggest candidate genes representing potential therapeutic targets for coronary artery disease.

Aim: In this study, we aim to analyze the correlation between brachial-ankle pulse wave velocity (baPWV) and Suita score or Framingham risk score and obtain the cutoff value of baPWV by sex and age for cardiovascular risk, as assessed by these scores in the large Japanese annual health checkup data.

Methods: In total, 25,602 participants (14,539 men and 11,063 women), who had their annual health checkups, were included in this study. Cutoff values of baPWV for the moderate- and high-risk groups stratified by sex and age were obtained using a receiver operating characteristic (ROC) curve analysis.

Results: As per our findings, the Suita score demonstrated better correlations with baPWV than the Framingham risk score in both sexes (men, Suita score R²=0.41 and Framingham risk score R²=0.37; women, Suita score R²=0.54 and Framingham risk score R²=0.33). The ROC curve analysis demonstrated the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score, and they are as follows: in men, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,520 cm/s in the 60s, and 1,880 cm/s in the 70s. In women, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,570 cm/s in the 60s, and 1,800 cm/s in the 70s.

Conclusions: We demonstrated that baPWV significantly correlated with the Suita score or Framingham risk score in both men and women, with the former presenting a stronger correlation than the latter. We propose the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score.

Aim: The Achilles tendon (AT) thickening may be affected by several factors (e.g., lipid disorders or age). This study aims to determine the prevalence rate of AT thickening in patients with coronary artery disease (CAD) and investigate the correlation between AT thickening and the incidence of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI).

Methods: The clinical records of 887 patients who had undergone successful PCI and measured Achilles tendon thickness (ATT) using soft X-ray radiographs were retrospectively examined. Subjects were divided into two groups depending on the presence or absence of AT thickening. AT thickening was defined as having ATT of ＞8.0 and ＞7.5 mm in men and women, respectively. Among the two groups, the incidence of MACE was measured for a maximum of 5 years after PCI. MACE was defined as cardiovascular mortality, nonfatal myocardial infarction, or revascularization due to restenosis or the increase of stenosis in other lesions.

Results: This study found that 241 (27.2%) patients have AT thickening. Patients with AT thickening had higher low-density lipoprotein cholesterol (LDL-C) levels. In addition, the Kaplan–Meier curve with a log-rank test demonstrated that patients with AT thickening had a significantly higher incidence of MACE. Furthermore, the multivariate analysis indicated that the presence of AT thickening was independently correlated with the incidence of MACE after PCI.

Conclusion: A high percentage of patients with CAD were found to have AT thickening. In addition, the presence of AT thickening was significantly associated with a higher incidence of MACE, independent of LDL-C levels.

Aims: The relationship between low body mass index (BMI) and prognostic factors for patients with coronary artery disease, commonly observed in elderly individuals in Japan, is important. Few studies have evaluated the prognosis for patients with low BMI after percutaneous coronary intervention (PCI). Using a multivariable-adjusted model and data from a prospective cohort registry, we analyzed the risk associated with low BMI for patients after PCI.

Methods: This prospective, multicenter registry included 5965 consecutive patients with coronary artery disease who underwent successful PCI. The patients were followed-up clinically for up to 3 years or until the occurrence of major adverse cardiac events. The primary endpoint was all-cause death and nonfatal myocardial infarction composite.

Results: Primary events occurred in 639 (10.7%) patients during the follow-up period. A risk analysis of the primary endpoint adjusted for the multivariable model showed a significant increase in risk for elderly individuals, underweight individuals [HR 1.43 (95% confidence interval (CI), 1.10–1.85), P＜0.001], those with diabetes mellitus (DM), peripheral artery disease, low left ventricular ejection fraction or acute coronary syndrome (ACS), and smokers. A stratified adjusted risk analysis based on BMI levels showed that the risk associated with underweight status was significantly pronounced for male patients, those aged 60–74 years, and those with DM or ACS.

Conclusion: Underweight patients with several risk factors significantly increased risk after PCI. Furthermore, the risk associated with low BMI was significantly more pronounced for men, individuals aged 60–74 years, and patients with DM or ACS.

Aim: In acute myocardial fraction (AMI) patients, the association between lipid parameters and new-onset atrial fibrillation (NOAF) remains unclear due to limited evidence.

Methods: A total of 4282 participants free from atrial fibrillation (AF) at baseline were identified in Beijing Friendship Hospital. Fasting levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured at baseline. The study population was stratified based on tertiles of lipid profile and lipid ratios. Incidence of NOAF was observed at the follow-up visits. The associations between different lipid parameters and the incidence of NOAF were assessed by multivariate Cox regression analysis.

Results: Over a median follow-up period of 42.0 months (IQR: 18.7, 67.3 months), 3.1% (N=132) AMI patients developed NOAF. After multivariable adjustment, higher TC (hazard ratios (HR): 0.205, 95% confidence intervals (CI): 0.061–0.696) levels were inversely associated with NOAF development. However, higher HDL-C (HR: 1.892, 95% CI: 1.133–3.159) levels were positively associated with NOAF development. LDL-C levels, TG levels, non-HDL-C levels, and lipid ratios showed no association with NOAF development.

Conclusion: TC levels were inversely associated with incidence of NOAF; this was mainly reflected in the subgroups of male gender and older patients (65 years or older). HDL-C levels were positively associated with incidence of NOAF; this was mainly reflected in the subgroups of male gender and younger patients (age ＜65 years). There was no significant association of NOAF with LDL-C, TG, or non-HDL-C levels.

As atherosclerosis begins in childhood, early diagnosis and treatment of familial hypercholesterolemia (FH) is considered necessary. The basic diagnosis of pediatric FH (under 15 years of age) is based on hyper-low-density lipoprotein (LDL) cholesterolemia and a family history of FH; however, in this guideline, to reduce overlooked cases, “probable FH” was established. Once diagnosed with FH or probable FH, efforts should be made to promptly provide lifestyle guidance, including diet. It is also important to conduct an intrafamilial survey, to identify family members with the same condition. If the level of LDL-C remains above 180 mg/dL, drug therapy should be considered at the age of 10. The first-line drug should be statin. Evaluation of atherosclerosis should be started using non-invasive techniques, such as ultrasound. The management target level is an LDL-C level of less than 140 mg/dL. If a homozygous FH is suspected, consult a specialist and determine the response to pharmacotherapy with evaluating atherosclerosis. If the response is inadequate, initiate lipoprotein apheresis as soon as possible.