Accumulating evidence suggests that conventional cardiovascular risk factors are incompletely predictive of cardiovascular disease, as a substantial risk remains even when these factors are apparently managed well. In this context, clonal hematopoiesis has emerged as a new and potent risk factor for atherosclerotic cardiovascular disease and other cardiometabolic conditions. Clonal hematopoiesis typically arises from somatic mutations that confer a competitive advantage to a mutant hematopoietic stem cell, leading to its clonal expansion in the stem cell population and its progeny of blood leukocytes. Human sequencing studies and experiments in mice suggest that clonal hematopoiesis, at least when driven by certain mutations, contributes to accelerated atherosclerosis development. However, the epidemiology, biology and clinical implications of this phenomenon remain incompletely understood. Here, we review the current understanding of the connection between clonal hematopoiesis and atherosclerosis, and highlight knowledge gaps in this area of research.

Background: This study aimed to identify the association between long term functional outcomes and acute ischemic stroke (AIS) in patients with heart failure (HF) in Japan and whether 1-year event risks can be related to these patients.

Methods and Results: This was a prospective observational study, and 651 patients registered in the Tokyo Women’s Medical University Stroke Registry were classified into the HF and non-HF groups. Functional outcome at 1 year after stroke onset was defined as either good (modified Rankin Scale [mRS] score of 0–2) or poor (mRS score of 3–6). The primary outcome was a composite of major adverse cardiovascular events (MACE), including non-fatal stroke, non-fatal acute coronary syndrome, and vascular death. Patients with HF had a higher poor functional outcome rate at 1 year than those without HF (54.7% vs. 28.2%, P<0.001). Multivariate logistic regression analysis also demonstrated the prevalence of HF was an independent predictor of an mRS score of ≥3 at 1 year after stroke onset (odds ratio, 1.05; 95% confidence interval, 1.00–1.10; P=0.036). Furthermore, patients with HF tended to have a higher risk of MACE and all-cause mortality than those without HF.

Conclusions: AIS patients with HF were associated with poor functional outcome at the 1-year follow up. Further multicenter studies involving a larger number of patients are warranted to verify these results.

Background: Although regenerative cell therapy is expected to be an alternative treatment for peripheral artery disease (PAD), many regenerative cell therapies have failed to show sufficient efficacy in clinical trials. Most preclinical studies have used acute ischemia models, despite PAD being a chronic disease. In addition, aging and atherosclerosis decrease the quality of a patient’s stem cells. Therefore, using a non-acute ischemic preclinical model and stem cells with high regenerative potency are important for the development of effective regenerative therapy. In this study, we assessed the tissue regenerative potential of umbilical cord-derived mesenchymal stromal cells (UCMSCs), which could potentially be an ideal cell source, in a rat model of established ischemia.

Methods and Results: The regenerative capacity of UCMSCs was analyzed in terms of angiogenesis and muscle regeneration. In vitro analysis showed that UCMSCs secrete high amounts of cytokines associated with angiogenesis and muscle regeneration. In vivo experiments in a rat non-acute ischemia model showed significant improvement in blood perfusion after intravenous injection of UCMSCs compared with injection of culture medium or saline. Histological analysis revealed UCMSCs injection enhanced angiogenesis, with an increased number of von Willebrand factor-positive microcapillaries, and improved muscle regeneration.

Conclusions: These results suggest that intravenous administration of UCMSCs may be useful for treating patients with PAD.

Background: Vessel preparation for endovascular treatment (EVT) is important but because the contributory factors for favorable outcomes are not yet known, we conducted the present study to elucidate the factors associated with sufficient vessel preparation for severely calcified femoropopliteal (FP) lesions.

Methods and Results: This was a single-center retrospective observational study of 97 patients (mean age, 75±8 years, 76% male) with 106 de novo severely calcified FP lesions who underwent EVT under intravascular ultrasound (IVUS) evaluation. The lesion definition was 360° of superficial calcification on IVUS. The primary outcome measure was sufficient vessel preparation, which was defined as successful cracking of severely calcified lesions evaluated by IVUS after predilation. The mean lesion length was 200±103 mm, and chronic total occlusion was present in 38% of patients. According to the greater difference between the preballoon size and the lumen diameter of the severely calcified lesion, the frequency of sufficient vessel preparation increased (odds ratio, 4.68; 95% confidence interval, 2.09–10.49; P<0.01). Balloon type (noncompliant, P=0.80; scoring: P=0.25) and pressure (P=0.27) were non-contributory.

Conclusions: The difference between the lumen diameter at the severely calcified FP lesion site and the preballoon dilatation diameter was the sole factor contributing to sufficient vessel preparation.

Background: Although favorable clinical outcomes have been demonstrated for fluoropolymer-based paclitaxel-eluting stents (FP-DES) in the treatment of femoropopliteal lesions, the vascular response after implantation has not been systematically studied through intravascular imaging.

Methods and Results: We angioscopically compared FP-DES: 24 in the early phase (mean [±SD] 3±1 months), 26 in the middle phase (12±3 months), and 20 in the late phase (≥18 months) after implantation. The dominant neointimal coverage grade, heterogeneity of neointimal coverage grade, and thrombus adhesion in the stent segment were evaluated. Neointimal coverage was graded as follows: Grade 0, stent struts exposed; Grade 1, struts bulging into the lumen, although covered; Grade 2, struts embedded in the neointima, but visible; Grade 3, struts fully embedded and invisible. Dominant neointimal coverage and heterogeneity grades were significantly higher in the middle and late phases than in the early phase (all P<0.05), but did not differ significantly between the middle and late phases. The incidence of thrombus adhesion was recorded for all stents in each of the 3 different phases.

Conclusions: The middle and late phases after FP-DES implantation were associated with significantly higher dominant neointimal coverage and heterogeneity grades than the early phase. However, thrombus adhesion was observed in all phases after FP-DES implantation. Arterial healing may not be completed even in the late phase after FP-DES implantation.

Background: We compared the location of the false lumen within the medial layer between acute intramural hematoma (AIH) and acute aortic dissection (AAD) using microscopic images of aortic specimens and examined the associations with patient characteristics, CT findings, and late outcomes.

Methods and Results: Among 293 patients undergoing surgery for Stanford type A acute aortic syndrome between 2008 and 2018, 45 patients had neither an identifiable intimal tear, flow to the false lumen on preoperative CT or intimal tear by intraoperative observation (AIH group), and 98 patients with patent false lumen were enrolled (AAD group). The AIH group had a significantly thinner outer media thickness (OMT) than the AAD group. The AIH group showed more pericardial effusion, but distal progression of dissection and branch vessel involvement were limited. The change in aortic diameter after surgery was insignificant in the AIH group, whereas in the AAD group it continued to increase. Cumulative incidence of aortic adverse events was significantly higher among AAD patients, but no significant difference was observed in survival between groups.

Conclusions: The AIH group had a significantly thinner OMT than the AAD group, which was significantly associated with a large amount of pericardial effusion, greater false lumen diameter, and limited progression of aortic dissection.

Background: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.

Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11–2.33, P=0.012), D-dimer levels >1.0 μg/mL on admission (OR: 2.10, 95% CI: 1.45–3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72–14.53, P<0.001) were independently associated with worsening of COVID-19 severity.

Conclusions: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 μg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.

Background: Previous studies investigating the relationship between hypertension (HT) and hematological parameters report inconsistent results, and most them included a small number of participants or only conducted a cross-sectional analysis of 1 or 2 hematological factors. Moreover, no large cohort follow-up studies have investigated this topic. The aim of this longitudinal study was to explore associations between components of the complete blood count (CBC) and incident HT using data from a large Taiwanese biobank

Methods and Results: Hematological parameters including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit (HCT), and platelet count were evaluated. We included 21,293 participants who did not have HT at baseline and followed them for a mean period of 3.9 years. During follow-up, 3,002 participants with new-onset HT (defined as incident HT) were identified. Univariable analysis revealed that high WBC count, high RBC count, high hemoglobin, high HCT, and low platelet count were associated with incident HT. Multivariable analysis after adjusting potential confounding factors found high WBC count (odds ratio [OR], 1.057; 95% confidence interval [CI], 1.028 to 1.087; P<0.001) and high HCT (OR, 1.023; 95% CI, 1.010 to 1.036; P<0.001) were still significantly associated with incident HT.

Conclusions: High WBC count and high HCT were associated with incident HT.