Journal of atherosclerosis and thrombosis最新文献

Aims: The Pemafibrate for Prevention of Atherosclerotic Diseases in Stroke (PPAR Stroke) study aimed to assess the effects of pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, on the progression of cerebrovascular atherosclerosis in patients with stroke and hypertriglyceridemia.

Methods: Ninety-nine patients (mean age, 65.6 years; male, 74.7%) with hypertriglyceridemia and a history of stroke or transient ischemic attack of non-cardioembolic origin were included in this prospective single-arm study. Hypertriglyceridemia was defined as a fasting serum triglyceride (TG) level ≥ 150 mg/dL. All patients were treated with pemafibrate (0.2 mg or 0.1 mg/day) for 2 years. The primary outcome was change in carotid intima-media thickness (IMT) from baseline at 2 years, as assessed using carotid ultrasonography. The secondary outcomes were changes in blood biomarker levels and progression of intracranial artery stenosis on magnetic resonance angiography.

Results: The mean TG level significantly decreased from 269 mg/dL at baseline to 139 mg/dL at 2 years (P＜0.001) and high-density lipoprotein cholesterol level increased from 49 to 54 mg/dL (P＜0.001), whereas low-density lipoprotein cholesterol level remained unchanged. Significant reductions in high-sensitivity C-reactive protein and interleukin-6 levels were also observed (P=0.003 and P=0.002, respectively). With regard to mean IMT in the internal carotid arteries, the difference was significant for the left side (1.59 mm at baseline vs. 1.52 mm at 2 years; P=0.009) and borderline significant for the right side (1.32 mm at baseline vs. 1.28 mm at 2 years; P=0.053). Among the 48 stenotic lesions in the intracranial arteries, regression and progression was observed in 9 (18.8%) and 4 (8.3%) cases, respectively.

Conclusions: Pemafibrate was observed to have TG-lowering and anti-inflammatory effects and could attenuate atherosclerosis progression in the intra- and extracranial arteries of patients with stroke and hypertriglyceridemia.

Aims: Clonal hematopoiesis of indeterminate potential (CHIP), which has recently been shown to be an age-related phenomenon, is associated with cardiovascular diseases, including atherosclerosis and stroke. This study focused on the association between CHIP and short- and long-term stroke recurrence in patients with acute ischemic stroke and intracranial atherosclerotic stenosis (ICAS).

Methods: This study included 4,699 patients with acute ischemic stroke based on data from the Third China National Stroke Registry (CNSR-III), a nationwide prospective hospital-based registry. The ICAS assessment followed the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease Study and Brain Imaging. Atherosclerosis Scores (AS) were used to assess the atherosclerosis burden, as determined by the number and severity of steno-occlusions in the intracranial arteries. The primary outcome was stroke recurrence three months and one year after the event.

Results: Among the 4,699 patients, 3,181 (67.7%) were female, and the median age was 63.0 (55.0-71.0) years. We found that CHIP significantly increased the risk of stroke recurrence at the 1-year follow-up in patients with ICAS (adjusted hazard ratio [HR] 2.71, 95% confidence interval [CI] (1.77-4.16), P for interaction, 0.008).

Conclusions: Our results revealed that CHIP might have a significant impact on the long-term risk of recurrent stroke, particularly in patients with a higher atherosclerotic burden.

Patients with chronic kidney disease (CKD) have a high incidence of atherosclerotic diseases, such as ischemic heart disease, cerebrovascular disease, and peripheral arterial disease. To prevent the incidence of atherosclerotic cardiovascular disease in patients with CKD, the pathology of arteriosclerosis should be determined. Vascular calcification is a characteristic of arteriosclerosis in patients with CKD. Recent studies have reported that coronary artery calcification is associated with acute coronary syndromes. CKD is frequently associated with heart failure. Furthermore, recent evidence suggests that coronary artery calcification affects asymptomatic myocardial ischemia. Hyperphosphatemia and calciprotein particles may be involved in the pathology of vascular calcification. Controlling the progression of vascular calcification and classical atherosclerotic risk factors is important to prevent the occurrence of atherosclerotic diseases in CKD.

Aim: Superficial erosion accounts for approximately one-third of all cases of acute coronary syndrome (ACS). Previously, we found that a nearby bifurcation is independently associated with superficial erosion; however, the effect of long-term oscillatory flow on superficial erosion remains unexplored. Endothelial-to-mesenchymal transition (EndMT) is a dynamic process in which endothelial cells acquire mesenchymal properties and, in turn, give rise to smooth muscle cell (SMC)-like cells and extracellular matrix (ECM) accumulation, similar to the autopsy pathology of superficial erosion. This finding prompted us to suspect that EndMT plays a role in the effect of chronic oscillatory flow on superficial erosion.

Methods: We established oscillatory flow in mouse carotid arteries and analyzed neointimal hyperplasia, endothelial continuity, ECM content, and EndMT markers 4 weeks later. Furthermore, bioinformatic data analyses and in vitro studies were performed to elucidate the underlying mechanisms.

Results: Carotid arteries exposed to long-term oscillatory flow exhibited hyperplastic neointima, reduced endothelial continuity, and increased SMC-like cells and ECM, indicating superficial erosion-prone lesions. In addition, oscillatory flow significantly induced EndMT, whereas inhibition of EndMT ameliorated the formation of superficial erosion-prone lesions. Bioinformatic data analyses and in vitro studies showed a remarkable reduction in anti-EndMT KLF2 and KLF4 in a DNA methyltransferase (DNMT)-dependent manner, and the suppression of DNMTs attenuated oscillatory flow-induced EndMT and superficial erosion-prone lesions.

Conclusions: Chronic oscillatory flow causes superficial erosion-prone lesions by activating EndMT in a DNMT-dependent manner. Our findings highlight a promising therapeutic strategy for the prevention of superficial erosions.

Aim: We examined the association between dairy intake and all-cause, cancer, and cardiovascular disease mortality in a cohort of the general population followed up for 12 years across Japan.

Methods: We conducted a longitudinal cohort study of 79,715 participants from the Japan Multi-Institutional Collaborative Cohort study (57.2% women, mean age 54.7 years old). The amount of dairy (milk and yogurt) intake was determined using a validated short-food frequency questionnaire. The hazard ratio for mortality according to sex-specific tertile of dairy intake was calculated using Cox proportional hazards regression models with adjustment for potential confounding factors and dietary factors by sex.

Results: During the follow-up period (932,738 person-years), 3,723 participants died, including 2,088 cancer and 530 cardiovascular disease deaths. The highest tertile of total dairy intake (versus the lowest tertile) was associated with a 19% lower all-cause mortality risk (hazard ratio=0.81, 95% confidence interval: 0.70-0.92; P for trend=0.001) in women. Similarly, we observed inverse associations between milk intake and all-cause and cancer mortality risk in women, yogurt intake and cardiovascular disease risk in women, and yogurt intake and all-cause mortality risk in both sexes.

Conclusion: A higher total dairy and milk intakes in women and yogurt intake in both sexes were associated with a reduced risk of all-cause mortality in the general population across Japan during the 12-year follow-up period.

Aim: Lipoprotein (a) [Lp(a)] is a well-established risk factor for cardiovascular disease independent of low-density lipoprotein-cholesterol (LDL-C). The Lp(a) concentrations were inconsistent between the immunoassays. This study aimed to investigate whether harmonization of Lp(a) measurements can be achieved using a serum panel value assigned with the IFCC-endorsed mass spectrometry-based reference measurement procedure (IFCC-MS-RMP).

Methods: We measured the Lp(a) concentrations using five Lp(a) immunoassays in 40 panel sera provided by the Centers for Disease Control and Prevention (CDC), and 500 Japanese subjects enrolled in the Bunkyo Health Study. Of the five immunoassays, only the Roche Lp(a) assay was traceable to the WHO-IFCC reference material SRM2B. Lp(a) concentrations in CDC samples were also determined by IFCC-MS-RMP, provisionally calibrated to SRM2B. Lp(a) concentrations were expressed in mass units (mg/dL) for most reagents, but in SI units (nmol/L) for Roche's reagent and IFCC-MS-RMP.

Results: In the CDC panel sera, all immunoassays, including Roche's reagent, showed good correlations with IFCC-MS-RMP. In the Bunkyo Health Study samples, all immunoassays showed good correlations with Roche's reagent (r_s, 0.986-0.998) although the slopes of the regression lines ranged from 0.292 to 0.579. After recalibration with the CDC's panel sera, Lp(a) results of Bunkyo Health Study samples were converted to the equivalent values determined by the IFCC-MS-RMP, thus resulting in a marked reduction in the intermethod CV among the assays.

Conclusion: We achieved harmonization of Lp(a) measurements with five immunoassays using a serum panel value assigned with the IFCC-MS-RMP.