Aims: Declines in cardiovascular diseases during the first surge of coronavirus disease 2019 (COVID-19) have been reported. With the repeating surges of COVID-19, we aim to investigate the medium-term impact of the COVID-19 pandemic on the practice of percutaneous coronary interventions (PCIs).

Methods: We performed a descriptive analysis of rates of PCIs, utilizing administrative data in Japan. Changes in the proportion of severe cases and in-hospital mortality since the start of the COVID-19 pandemic were investigated using interrupted time series (ITS) analyses.

Results: From April 2018 to February 2021, 38,696 and 28,585 cases of elective and emergency PCIs, respectively, were identified. The rates of PCIs decreased during the first and third COVID-19 surges. The ratios of monthly rates of elective PCIs to that in the corresponding months during the previous 2 years were 50.3% in May 2020 and 76.1% in January 2021. The decrease in rates of emergency PCIs was smaller than that of elective PCIs. The ITS analyses did not identify any significant changes in the proportion of severe cases and in-hospital mortality.

Conclusions: We found that the impacts of COVID-19 on PCIs were larger in the first surge than in the subsequent and larger in the elective than in the emergency; this continued over the medium-term. During the COVID-19 pandemic, in-hospital mortality of cases undertaking emergency PCIs did not change.

Aim: An experimental study showed that potassium inhibits the formation of reactive oxygen species by vascular cells. The purpose of this study was to investigate the association between serum potassium levels and vascular function.

Methods: We measured flow-mediated vasodilation (FMD) as an index of endothelial function in 3045 subjects (1964 men; mean age, 62.3±13.8 years) and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function in 1578 subjects (1001 men; mean age, 61.8±16.3 years).

Results: In the 3045 subjects, there was a significant positive correlation between FMD and serum potassium levels (r=0.09, P＜0.001). Multivariate analysis revealed that serum potassium levels were significantly associated with FMD (β=0.109, P＜0.001). When subjects were divided into two groups based on treatment with drugs that could alter serum potassium levels, the association between serum potassium levels and FMD was significant both in subjects with (β=0.096, P＜0.001) and subjects without (β=0.123, P＜0.001) treatment with drugs that could alter serum potassium levels. In the 1578 subjects, there was a significant positive correlation between NID and serum potassium levels (r=0.11, P＜0.001). Multivariate analysis revealed that serum potassium levels were significantly associated with NID (β=0.098, P＜0.001). The association between serum potassium levels and NID was significant both in subjects with (β=0.121, P=0.001) and subjects without (β=0.083, P=0.03) treatment with drugs that could alter serum potassium levels.

Conclusions: Serum potassium levels of 4.5-＜5.0 mmol/L are associated with better vascular function regardless of the presence or absence of treatment with drugs that could alter serum potassium levels.

Aims: Achilles tendon (AT) xanthomas are a specific physical finding of familial hypercholesterolemia (FH) and AT thickness has been used for its diagnosis and evaluation of its severity. Recently, we reported that the AT of FH patients was softer than that of non-FH patients and the combined use of a cut-off value for AT softness with that for AT thickness improved diagnostic accuracy. However, an association between AT softness and severity of atherosclerosis has not been reported. Accordingly, the present study aimed to investigate whether AT softness was associated with carotid atherosclerosis and presence of atherosclerotic cardiovascular disease (ASCVD) in FH.

Methods: The AT of 176 genetically diagnosed FH patients and 98 non-FH patients was examined to measure AT thickness and the elasticity index (EI) as an indicator for assessing AT softness using ultrasonography.

Results: Increased age was associated with AT softness, and overweight was negatively related to AT softness. There were significant inverse correlations between EI and maximum and mean intima-media thickness (IMT) within the common carotid artery only among FH patients. In multiple linear regression analysis, although the relationship between EI and mean IMT was attenuated, the association between EI and maximum IMT remained robust. In logistic regression analysis adjusted for age, sex and traditional cardiovascular risk factors (smoking history, presence of hypertension, presence of diabetes mellitus, overweight, LDL-cholesterol, HDL-cholesterol, and Log triglycerides), EI was associated with presence of ASCVD (Odds ratio per 1-SD increase, 0.37; 95% CI, 0.15 – 0.86; P=0.0252).

Conclusion: The degree of lipid deposition in the AT of FH patients could be assessed by its thickness as well as its softness. AT softness is not only useful in diagnosing FH but is also associated with the severity of carotid atherosclerosis and presence of ASCVD. In addition, these findings suggest that AT softness would be helpful in risk assessment for FH patients.

Aims: Mechanical thrombectomy using a standard device has been effective for acute cerebral large-vessel occlusions, particularly those due to cardiogenic embolism. However, evidence for those with underlying atherosclerotic lesions is lacking. In this study, we evaluated the predictive factors, treatment details, and outcomes of acute cerebral large-vessel occlusions with underlying atherosclerotic lesions in patients who underwent mechanical thrombectomy.

Methods: We retrospectively analyzed consecutive patients with acute large-vessel occlusions who underwent mechanical thrombectomy at our institution between August 2014 and May 2021. Predictive factors of underlying atherosclerotic lesions were evaluated using univariate and multivariate analyses. In addition, treatment details and outcomes were evaluated and compared with those of other etiologies.

Results: Among 322 included patients, 202 (62.7%) were males and 65 (20.2%) had underlying atherosclerotic lesions. Multivariate analysis identified dyslipidemia, lack of arterial fibrillation documented on admission, smoking, internal carotid artery lesions, and stenosis ≥ 25% in non-occluded large vessels as predictive factors of underlying atherosclerotic lesions. Regarding treatment for underlying atherosclerotic lesions, the need for percutaneous transluminal angioplasty, stent placement, medical therapy, and longer procedure time were observed, while successful reperfusion rates, favorable outcomes, and mortality rates showed no significant differences with those of other etiologies.

Conclusion: Coexisting diseases and radiological findings were useful for predicting underlying atherosclerotic lesions. Further understanding these characteristics may lead to the early detection of underlying atherosclerotic lesions, optimal treatment strategies, and better outcomes.

Aims: High platelet reactivity (HPR) has been associated with an increased risk of thrombotic events in patients undergoing percutaneous coronary intervention. HPR has been well examined in patients treated with clopidogrel; however, HPR on prasugrel is poorly investigated.

Methods: Four prospective studies were pooled, in which platelet reactivity on prasugrel was measured using VerifyNow assay; genotyping of CYP2C19 was also performed. Factors associated with HPR on prasugrel were identified using multivariable analysis to develop a risk prediction model.

Results: In total, 180 patients were examined in this study, of whom 51 (28%) had HPR on prasugrel. The multivariable analysis indicated that hypertension, diabetes, hemodialysis, and the number of CYP2C19 loss-of-function (LOF) alleles are significant factors for HPR on prasugrel. These four factors were then incorporated to develop the HHD-GENE score. The receiver operating characteristic curve analysis showed that the HHD-GENE score predicted HPR on prasugrel (area under the curve (AUC) 0.74, best cutoff value 5, p＜0.001). With the best cutoff value, patients with the HHD-GENE score ≥ 5 had a significantly increased risk of HPR on prasugrel than their counterpart (50% vs. 18%, p＜0.001).

Conclusions: The HHD-GENE score consisting of hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles may be useful in identifying patients on prasugrel who are at high risk for HPR. External validation is needed to define the clinical utility of this novel scoring system.

Aims: Residual inflammation risk refers to inflammation that still increases the risk of cardiovascular disease after the level of low-density lipoprotein cholesterol (LDL-C) reached the target (＜70 mg/dL). However, whether inflammation is still an important issue even if very low LDL-C levels have been achieved remains unclear. This study aimed to investigate the contribution of inflammation to stroke recurrence on different LDL-C levels following ischemic stroke (IS) or transient ischemic attack (TIA).

Methods: A total of 10499 IS/TIA patients whose LDL-C and high-sensitivity C-reactive protein (hsCRP) were measured were selected from the Third China National Stroke Registry. The cutoff values were set to 25, 35, 45, 55, 70, and 100 mg/dL for LDL-C, whereas the threshold values of hsCRP and interleukin-6 (IL-6) were 2 mg/L and 1.65 ng/L, respectively. Based on each group of LDL-C, Cox regressions were conducted to investigate the associations between inflammation and recurrent stroke within 1 year.

Results: The associations between baseline hsCRP levels and stroke recurrence were non-significant in groups with LDL-C ＜55 mg/dL (P＞0.05). After stratification by baseline LDL-C of 55 mg/dL, hsCRP ≥ 2 mg/L (10.9% versus 7.5%, P＜0.0001) and IL-6 ≥ 1.65 ng/L (9.8% versus 7.4%, P=0.0002) were found to be related to a high incidence of recurrent IS among patients with LDL-C ≥ 55 mg/dL; however, no associations were observed among patients with LDL-C ＜55 mg/dL. Compared with low inflammation (both hsCRP ＜2 mg/L and IL-6 ＜1.65 ng/L), high inflammation (both hsCRP ≥ 2 mg/L and IL-6 ≥ 1.65 ng/L) was significantly associated with stroke recurrence when LDL-C ≥ 55 mg/dL (adjusted HR 1.38, 95% CI 1.10–1.74), whereas this association was not observed when LDL-C ＜55 mg/dL (adjusted HR, 0.72; 95% CI, 0.41–1.25).

Conclusion: For IS/TIA patients, the contribution of inflammation to stroke recurrence seems to be attenuated at a low level of LDL-C.

Aim: Acute kidney injury (AKI) is an important clinical issue in the diagnosis and treatment of cardiovascular diseases. The association between pretreatment by statins and the occurrence of AKI in patients with peripheral arterial diseases (PAD) remains unclear. Therefore, we examined the association between statin therapy and the occurrence of AKI in patients with PAD.

Methods: We retrospectively analyzed data from the endovascular treatment (EVT) database in our hospital. A total of 295 patients who underwent angiography and/or intervention for PAD between October 2011 and March 2016 were enrolled and divided into two groups: those without statins (control group; N=157) and those with statins (statin group; N=138) for at least 1 month before admission. We examined the occurrence of AKI and its related factors in these patients.

Results: The serum creatinine levels, dose of contrast medium, use of a renin-angiotensin system inhibitor, smoking habit, and blood pressure were similar in both groups. The statin group had more diabetes patients, had patients who were significantly younger, had patients with a higher body mass index (BMI), and had patients with lower low-density lipoprotein cholesterol than the control group. With regard to the occurrence of AKI, there was a significantly lower incidence in the statin group compared with the control group (5% vs. 16%, p＜0.05). The result of the multivariate analysis indicated that statin therapy was significantly correlated with lower occurrence rates of AKI (p＜0.05).

Conclusions: Our study suggests that statin therapy might prevent the occurrence of AKI after angiography and/or intervention for PAD.

Aim: The ring finger protein 213 gene (RNF213) p.R4810K variant is a major susceptibility gene for intracranial arterial stenosis in East Asia. We hypothesized that if intracranial arterial stenosis is induced by a non-atherosclerotic mechanism similar to moyamoya disease, the patients with RNF213 p.R4810K variant may have a lower cumulative atherosclerotic burden than the non-carriers.

Methods: A total of 112 participants with intracranial arterial stenosis were enrolled in this multicenter cross-sectional study. We compared the prevalence of atherosclerotic risk factors and three different cardiovascular risk scores (Essen Stroke Risk Score, Framingham Risk Score, and Suita Risk Score) between the RNF213 p.R4810K variant carriers and non-carriers. Patients with moyamoya disease were excluded from the study.

Results: The RNF213 p.R4810K variant carriers were younger than the non-carriers (P＜0.001). The prevalence of each atherosclerotic risk factor was not significant, but it tended to be lower in the variant carriers. The Essen Stroke Risk Score (carriers: 2.3±1.5 vs. non-carriers: 2.9±1.5, P=0.047), Framingham Risk Score (10.7±6.4 vs. 15.3±6.2, P=0.001), and Suita Risk Score (35.4±15.8 vs. 48.7±15.2, P＜0.001) were significantly lower in the variant carriers. Among the three risk scores, the Suita score showed the highest predictive accuracy for the variant carriers.

Conclusions: RNF213 p.R4810K variant carriers have a lower cumulative atherosclerotic burden than non-carriers among patients with intracranial arterial stenosis. New therapeutic approaches beyond the standard management of atherosclerotic risk factors are required to prevent the development of intracranial arterial stenosis.

Aims: This study aimed to investigate the association of mild hypertensive retinopathy with cardiovascular disease (CVD) risk.

Methods: A total of 7,027 residents aged 30–79 years without a history of CVD participated in the annual health checkups and retinal photography assessments. Retinal microvascular abnormalities were graded using the standard protocols and classified according to the Keith–Wagener–Barker classification. Mild hypertensive retinopathy was defined as grades 1 and 2. Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for total CVD and its subtypes according to the presence and absence of mild hypertensive retinopathy.

Results: During a median follow-up of 17 years, 351 incident stroke and 247 coronary heart disease (CHD) cases were diagnosed. After adjustment for traditional cardiovascular risk factors, mild hypertensive retinopathy was positively associated with risk of CVD (multivariable HR=1.24; 95% CI, 1.04–1.49) and stroke (1.28; 1.01–1.62) but not with risk of CHD (1.19; 0.89–1.58). Generalized arteriolar narrowing and enhanced arteriolar wall reflex were positively associated with CVD risk, the multivariable HR (95% CI) was 1.24 (1.00–1.54) and 1.33 (1.02–1.74), respectively. Moreover, mild hypertensive retinopathy was positively associated with stroke risk in normotensive participants.

Conclusion: Mild hypertensive retinopathy was positively associated with CVD and stroke risk in the urban Japanese population. Especially, generalized arteriolar narrowing and enhanced arteriolar wall reflex were positively associated with CVD risk. These findings suggested that retinal photography could be helpful for cardiovascular risk stratification in the primary cardiovascular prevention.

Aims: Serum uric acid increases with metabolic disorders; however, whether the effects of uric acid on atherosclerosis are different in females and males has not been sufficiently evaluated. Therefore, this study compared the impact of uric acid on arterial stiffness and atherosclerosis between females and males.

Methods: We enrolled 10196 untreated middle-aged subjects (46±8 years, 3021 females and 7175 males) who underwent periodic health check-ups. Serum uric acid levels were measured and arterial stiffness and atherosclerosis were assessed by the cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and plaque, using ultrasound imaging.

Results: Females with increased arterial stiffness (CAVI ≥ 8.0) or carotid plaques had higher uric acid than those without (P＜0.0001), but males did not. In multivariable regression analyses including overall participants, uric acid was significantly associated with the CAVI, where sex interacted with uric acid. In sex-specific analyses, uric acid was significantly associated with the CAVI, but not with carotid IMT, in both sexes. However, logistic regression analyses revealed that serum uric acid was independently associated with the presence of carotid plaques in females. The exclusion of subjects with abdominal obesity or metabolic syndrome from the analysis did not alter the results in females.

Conclusions: Serum uric acid was significantly associated with the CAVI in both sexes, but the interaction of sex was confirmed and associated with a carotid plaque only in females. These findings support the increased impact of serum uric acid on arterial stiffness and atherosclerosis in females.