Aim: Circulating omega-3 and omega-6 polyunsaturated fatty acids may to contribute to cardiovascular health at the population level. Over a decade, we investigated changes in the serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio, and in serum concentrations of the individual fatty acids, in a Japanese community.

Methods: Community surveys took place in 2002–2003 and 2012–2013 in a rural area of Japan. The community surveys included 3,194 and 3,220 community dwellers aged ≥ 40 years who did not take EPA medication in 2002–2003 and 2012–2013, respectively. Fatty acid fractionations in serum were measured using a gas chromatography method. Changes in the serum EPA/AA ratio over time were examined using linear mixed models.

Results: Overall, the average serum EPA/AA ratio decreased over the 10 years. A decreasing trend in the serum EPA/AA ratio occurred in all age groups except participants aged ≥ 80 years, with larger decreases in the younger age groups. A similar decline in serum EPA/AA ratio occurred in participants with and those without lipid-lowering therapy. Serum EPA concentrations were slightly increased in the whole population but remained stable or even decreased in participants aged 40–69. In contrast, the average serum AA concentrations increased in all age groups.

Conclusion: In a Japanese community, the serum EPA/AA ratio decreased over 10 years at the population level, especially in middle-aged participants.

Aim: This study aimed to investigate the relationship between symptomatic or asymptomatic intracranial/extracranial artery stenosis and high-sensitivity C-reactive protein (hs-CRP) levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).

Methods: This study included 10404 patients from the Third China National Stroke Registry. Patients were divided into four or six groups according to patterns of intracranial or extracranial artery stenosis and hs-CRP levels. The outcomes were recurrence of ischemic stroke, stroke, and combined vascular events (CVE) at 1 year. The associations between different combinations of hs-CRP levels and patterns of artery stenosis and recurrent events were analyzed by multivariable Cox regression models.

Results: Patients in Group III (hs-CRP ＜3＋symptomatic intracranial or extracranial artery stenosis) had higher risk of recurrent ischemic stroke (adjusted hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.20–2.48, p=0.003). Those in Group VI (hs-CRP ≥ 3＋symptomatic intracranial or extracranial artery stenosis) had the highest risk of recurrent ischemic stroke (HR 2.04, 95% CI 1.42–2.92, p=0.0001) within 1 year compared with Group I (hs-CRP ＜3＋no artery stenosis). Asymptomatic intracranial or extracranial artery stenosis did not increase the risk of ischemic events compared with no artery stenosis regardless of hs-CRP levels.

Conclusion: Symptomatic intracranial or extracranial artery stenosis was associated with increased risk of recurrent ischemic stroke, stroke, and CVE at 1 year in patients with AIS or TIA, especially in patients with elevated hs-CRP levels. Asymptomatic intracranial or extracranial artery stenosis did not increase the risk of ischemic events compared with no artery stenosis regardless of hs-CRP levels.

Aim: Apolipoprotein E (ApoE) strongly affects arteriosclerosis but has atheroprotective effects in combination with high-density lipoprotein cholesterol (HDL-C). The impact of the quantitative relationship between serum ApoE and HDL-C levels in patients with coronary artery disease (CAD) remains unclear.

Methods: A total of 3632 consecutive patients who underwent their first intervention between 2000 and 2016 were included. They were categorized into normal and abnormal HDL-C groups based on the normal HDL-C value, and each group was subdivided into high and low ApoE subgroups based on the group-specific median ApoE value. We evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and all-cause death

Results: During a 6.4-year follow-up, 419 patients developed MACCE and 570 patients died. The interaction term between ApoE levels and HDL-C status in MACCE and all-cause death proved to be statistically significant. Kaplan–Meier analysis revealed that the cumulative incidence of MACCE was significantly higher for elevated pre-procedural ApoE levels than for reduced preprocedural ApoE levels in the normal HDL-C group. Conversely, the cumulative incidence of MACCE was significantly higher for reduced pre-procedural ApoE levels than for elevated pre-procedural ApoE levels in the abnormal HDL-C group. After adjustment for important covariates, multivariable Cox hazard analysis revealed that the serum ApoE level was a strongly independent predictor of MACCE; this was inversely related in both groups.

Conclusions: Serum ApoE levels may have a paradoxical impact on the future cardiovascular risk depending on the HDL-C status in patients with CAD.

Aim: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19).

Method: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20–39, 40–59, 60–79, and 80- years.

Results: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20–39, 40–59, 60–79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity.

Conclusions: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission.

Aims: Carotid reocclusion (CRO) after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to tandem lesion (TL) or isolated internal carotid occlusion (ICO) is associated with worse clinical outcomes. Our aim was to analyze the predictors and clinical impact of CRO.

Methods: A retrospective single-center analysis of all patients with anterior circulation strokes who underwent MT prospectively included in a registry between 2017 and 2020 was performed. ICO and TL as stroke causes were included. Stent deployment was left to the discretion of the interventionist. All patients received at least intravenous aspirin during MT. CRO was assessed using ultrasound within the first 24 h after MT. Efficacy and safety of stenting were assessed.

Results: Among 1304 AIS cases, 218 (16.7%) were related to TL or ICO. Of them, 5% (n=11) were associated with internal CRO 24 h after the endovascular procedure. After adjusting per confounders, multivariate analysis showed that the independent variables associated with CRO were the TICI recanalization grade [TICI 2b–3; OR 0.1, 95% confidence interval (CI) 0.01–0.89, p=0.040], pial collateral circulation presence (OR 0.09, 95% CI 0.02–0.45, p=0.03), stent deployment during MT (OR 0.17, 95% CI 0.03–0.84, p=0.030), and general anesthesia use (OR 2.92, 95% CI 1.13–7.90, p=0.034). CRO showed a trend toward worst outcomes (modified Rankin scale 3–6) at 3 months (OR 3.4, 95% CI 0.96–12, p=0.057). After multivariate analysis, variables independently associated with worse outcomes at 90 days were intrastent platelet aggregation phenomena during endovascular therapy, admission National Institute of Health Stroke Scale, and age. Conversely, intravenous thrombolysis and TICI 2b–3 recanalization grade were identified as independent predictors of good outcomes at 90 days.

Conclusions: CRO has a relevant clinical impact in our study, associating lower rates of good functional outcomes at 3 months. Independent factors of CRO were the recanalization degree, presence of pial collateral circulation, use of a stent as a protective factor, and use of general anesthesia during thrombectomy.

Aims: Calcified nodule (CN) has been known as the advanced stage of coronary calcification. However, clinical outcomes following percutaneous coronary intervention (PCI) to CN remain unknown. This study aimed to compare clinical outcomes, including target lesion revascularization (TLR), between calcified coronary lesions with and without CN.

Methods: Two hundred forty-nine lesions undergoing intravascular ultrasound-guided PCI with rotational atherectomy (RA) were enrolled and divided into the CN group (n=100) and the non-CN group (n=149) according to the presence of CN. The cumulative incidence of clinically driven TLR (CD-TLR) and the reasons for CD-TLR were compared between the CN and non-CN groups.

Results: The incidence of CD-TLR was significantly higher in the CN group than in the non-CN group. In the landmark analysis at 1 year, the CN group showed a significantly higher incidence of CD-TLR within 1 year. However, the incidence of CD-TLR beyond 1 year was numerically lower in the CN group than in the non-CN group. In the multivariate Cox hazard model, CN was significantly associated with CD-TLR. In the CN group, in-stent CN was the major reason for CD-TLR (52%) and was observed mainly within 1 year (90%).

Conclusions: In the heavily calcified lesions requiring RA, CN was the factor associated with the higher rate of CD-TLR especially within 1 year. The timing of CD-TLR in lesions with CN may indicate that the process of CN protruding through the struts was progressed monthly.

Aims: This study aimed to investigate the long-term impact of guideline-directed medical therapy (GDMT) on 10-year mortality in patients with chronic limb-threatening ischaemia (CLTI) after revascularization.

Methods: We performed a retrospective multicentre study enrolle 459 patients with CLTI who underwent revascularization (396 endovascular therapy [EVT] and 63 bypass surgery [BSX] cases) between January 2007 and December 2011. The primary outcome measure was all-cause mortality. We additionally explored the predictors for all-cause mortality using Cox regression hazard models; the influence of GDMT, defined as prescription of antiplatelet agents, statins, and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in aggregate, on all-cause mortality, and the association between baseline characteristics using interaction effects.

Results: During the 10-year follow-up after revascularization, 234 patients died. In Kaplan-Meier analysis, 10-year mortality was significantly lower in patients who received statins (p＜.001) and ACE inhibitors or ARBs (p=.010) than those who did not. However, there were no differences in 10-year mortality between patients who received anti-platelet agents and those who did not (p=.62). Interaction analysis revealed that GDMT had a significantly different hazard ratio in patients who were and were not on hemodialysis and in those treated with EVT or BSX (p for interaction =.002 and .044, respectively). In the multivariate analysis, age ＞75 years, non-ambulatory status, hemodialysis, congestive heart failure, left ventricular ejection fraction ＜50%, and GDMT were significantly associated with all-cause mortality.

Conclusions: Appropriate GDMT use was independently associated with 10-year mortality in patients with CLTI after revascularization.

Aim: Although some sex differences in stroke have been reported, differences in the effects of antiplatelet therapy for secondary stroke prevention have not been clarified.

Methods: In the Cilostazol Stroke Prevention Study combination trial, patients with high-risk, non-cardioembolic ischemic stroke between 8 and 180 days after onset treated with aspirin or clopidogrel alone were recruited and randomly assigned to receive either monotherapy or dual antiplatelet therapy (DAPT) using cilostazol and followed up for 0.5–3.5 years. The primary efficacy outcome was recurrence of ischemic stroke. The safety outcome was severe or life-threatening hemorrhage. Outcomes were analyzed by sex.

Results: A total of 1,320 male patients and 558 female patients were included. The male patients had more risk factors than the female patients. In male patients, the primary endpoint occurred at a rate of 2.0 per 100 patient-years in the DAPT group and 5.1 per 100 patient-years in the monotherapy group (hazard ratio (HR), 0.40; 95% confidence interval (CI), 0.23–0.68). In male patients, DAPT prolonged the time to recurrent stroke by 4.02-fold (95% CI, 1.63–9.96) compared with monotherapy. In female patients, the average annual event rates were 2.7 per 100 patient-years in the DAPT group and 3.3 per 100 patient-years in the monotherapy group (HR, 0.82; 95% CI, 0.37–1.84). Safety outcomes did not differ significantly in both male and female patients.

Conclusions: Long-term DAPT using cilostazol reduced the recurrence of ischemic stroke and prolonged the recurrence-free time in male patients, but not in female patients.

Aim: Vascular endothelial function and atherosclerosis are known to be important risk factors for cardiovascular disease. However, it remains unknown whether remnant cholesterol (RC) correlates with vascular endothelial function and atherosclerosis as represented by flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV). Therefore, in this study, we aimed to investigate this in the general population.

Methods: In this study, we examined 13,237 subjects who have undergone blood lipid, FMD, and baPWV measurements. Participants were divided into four groups based on RC quartiles. Multivariable linear regression models were used to calculate odds ratios for FMD and baPWV according to the RC levels.

Results: A significant negative relationship was found between RC and FMD (β=−0.14, p=0.014), whereas RC was positively associated with baPWV (β=21.42, p＜0.001), especially in the male and without chronic disease medication populations. The population was divided into three groups according to their lipids: dyslipidemia group, nondyslipidemia but RC increased group (RC ＞0.78 mmol/L), and nondyslipidemia and RC normal group (RC ≤ 0.78 mmol/L). The FMD of the three groups was 7.09%±3.36%, 7.39%±3.38%, and 7.57%±3.54%, respectively. The baPWV of the three groups was 1445.26±261.56 cm/s, 1425.04±265.24 cm/s, and 1382.73±267.75 cm/s. Significant differences were noted between the groups.

Conclusions: The findings indicated that a higher RC was an independent predictive factor for participants with endothelial function and atherosclerosis. It is important to use RC as a risk management indicator of vascular function, especially for those with normal conventional lipid parameters but increased RC.