Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 85 , Issue 6
Showing 1-36 articles out of 36 articles from the selected issue
Focus on issue: Ischemic Heart Disease
Reviews
  • Albert Youngwoo Jang, Soo Lim, Sang-Ho Jo, Seung Hwan Han, Kwang Kon K ...
    Type: REVIEW
    2021 Volume 85 Issue 6 Pages 759-768
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: November 12, 2020
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    Dyslipidemia is one of the most important risk factors for cardiovascular (CV) disease. Statin therapy has dramatically improved CV outcomes and is the backbone of current lipid-lowering therapy, but despite well-controlled low-density lipoprotein cholesterol (LDL-C) levels through statin administration, up to 40% patients still experience CV disease. New therapeutic agents to tackle such residual cholesterol risk by lowering not only LDL-C but triglycerides (TG), TG-rich lipoproteins (TRL), or lipoprotein(a) (Lp(a)) are being introduced. Ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, PCSK9 small interference RNA (siRNA), and bempedoic acid added to statin therapy have shown additional improvement to CV outcomes. Recent trials administering eicosapentaenoic acid to patients with high TG despite statin therapy have also demonstrated significant CV benefit. Antisense oligonucleotide (ASO) therapies with hepatocyte-specific targeting modifications are now being newly introduced with promising lipid-lowering effects. ASOs targeting TG/TRL, such as angiopoietin-like 3 or 4 (ANGPTL3 or ANGPTL4), apolipoprotein C-III (APOC3), or Lp(a) have effectively lowered the corresponding lipid profiles without requiring high or frequent doses. Clinical outcomes from these novel therapeutics are yet to be proven. Here, we review current and emerging therapeutics targeting LDL-C, TG, TRL, and Lp(a) to reduce the residual CV risk.

Original Articles
Antithrombotic Therapy
  • Masahiro Natsuaki, Takeshi Morimoto, Hiroki Shiomi, Natsuhiko Ehara, R ...
    Type: ORIGINAL ARTICLE
    Subject area: Antithrombotic Therapy
    2021 Volume 85 Issue 6 Pages 769-781
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: December 08, 2020
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    Supplementary material

    Background:The prevalence of and expected bleeding event rate in patients with the Japanese version of high bleeding risk (J-HBR) criteria are currently unknown in real-world percutaneous coronary intervention (PCI) practice.

    Methods and Results:We applied the J-HBR criteria in the multicenter CREDO-Kyoto registry cohort-3 that enrolled 13,258 consecutive patients who underwent first PCI. The J-HBR criteria included Japanese-specific major criteria such as heart failure, low body weight, peripheral artery disease and frailty in addition to the Academic Research Consortium (ARC)-HBR criteria. There were 8,496 patients with J-HBR, and 4,762 patients without J-HBR. The J-HBR criteria identified a greater proportion of patients with HBR than did ARC-HBR (64% and 48%, respectively). Cumulative incidence of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the J-HBR group than in the no-HBR group (14.0% vs. 4.1% at 1 year; 23.1% vs. 8.4% at 5 years, P<0.0001). Cumulative 5-year incidence of BARC 3/5 bleeding was 25.1% in patients with ARC-HBR, and 23.1% in patients with J-HBR. Cumulative incidence of myocardial infarction or ischemic stroke was also significantly higher in the J-HBR group than in the no-HBR group (6.9% vs. 3.6% at 1 year; 13.2% vs. 7.1% at 5 years, P<0.0001).

    Conclusions:The J-HBR criteria successfully identified those patients with very high bleeding risk after PCI, who represented 64% of patients in this all-comers registry.

  • Kengo Tanabe
    Type: EDITORIAL
    2021 Volume 85 Issue 6 Pages 782-784
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: January 27, 2021
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  • Masato Nakamura, Kazushige Kadota, Koichi Nakao, Yoshihisa Nakagawa, J ...
    Type: ORIGINAL ARTICLE
    Subject area: Antithrombotic Therapy
    2021 Volume 85 Issue 6 Pages 785-793
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: February 11, 2021
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    Supplementary material

    Background:Outcomes with prasugrel single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT) in Japanese percutaneous coronary intervention (PCI) patients with high bleeding risk (HBR) are currently unknown.

    Methods and Results:Data from 1,173 SAPT and 2,535 DAPT patients from the PENDULUM mono and PENDULUM registry studies (respective median DAPT durations: 108 vs. 312 days) were compared. The adjusted cumulative incidence of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding from 1 to 12 months after PCI (primary endpoint) was 2.8% (95% confidence interval [CI], 1.9–4.2) and 4.1% (95% CI, 3.3–5.1), respectively (hazard ratio [HR], 0.69; 95% CI, 0.45–1.06; P=0.090). The adjusted cumulative incidences of BARC 2, 3, or 5 bleeding from 0 to 12 months after PCI (secondary endpoint) were 3.8% (95% CI, 2.7–5.3) and 5.6% (95% CI, 4.7–6.7), respectively (HR, 0.68; 95% CI, 0.47–0.98; P=0.039). There was no significant difference in major adverse cardiac and cerebrovascular events (MACCE) from 1 to 12 months after PCI (HR, 0.93; 95% CI, 0.63–1.37; P=0.696) and at 12 months after PCI (HR, 0.85; 95% CI, 0.61–1.19; P=0.348) between the groups.

    Conclusions:Prasugrel SAPT may reduce BARC 2, 3, or 5 bleeding, without increasing MACCE, in Japanese patients with HBR.

  • Masahiro Natsuaki, Koichi Node
    Type: EDITORIAL
    2021 Volume 85 Issue 6 Pages 794-796
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: February 18, 2021
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  • Katsuya Miura, Yuki Shima, Koya Okabe, Yuya Taguchi, Akihiro Ikuta, Ko ...
    Type: ORIGINAL ARTICLE
    Subject area: Antithrombotic Therapy
    2021 Volume 85 Issue 6 Pages 797-805
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: April 14, 2021
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    Supplementary material

    Background:The validity of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definitions of early (<1 year), late (1–4 years), and very late (>4 years) bleeding events is unknown.

    Methods and Results:This study was performed on patients (n=3,453) implanted with second-generation drug-eluting stents (DES) between 2010 and 2013. Data on all criteria of the ARC-HBR definition were collected retrospectively. The primary endpoint was Bleeding Academic Research Consortium Type 3 or 5 bleeding events; the ischemic endpoint was a composite of cardiac death, myocardial infarction, and ischemic stroke. The mean follow-up period was 7.5 years. Compared with non-high bleeding risk (HBR) patients, HBR patients (n=1,840; 53.3%) had an increased risk of the primary endpoint (early events, 3.6% vs. 0.5% [P<0.0001]; late events, 5.3% vs. 2.5% [P<0.0001]; very late events, 5.5% vs. 2.1% [P<0.0001]) and of ischemic events during follow-up. The discrimination ability of the ARC-HBR definition for late and very late bleeding events was comparable to that of early bleeding events (C statistics 0.679, 0.621, and 0.620, respectively) with high negative predictive value (96.6%, 95.1%, and 93.1%, respectively). Multivariate analysis revealed the different effects of individual criteria on bleeding events in each follow-up period.

    Conclusions:The ARC-HBR definition consistently identified patients at risk of long-term bleeding and ischemic events after second-generation DES implantation.

  • Yuichi Saito, Yoshio Kobayashi
    Type: EDITORIAL
    2021 Volume 85 Issue 6 Pages 806-807
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: April 15, 2021
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  • Takayoshi Toba, Toshiro Shinke, Hiromasa Otake, Hiroyuki Kawamori, Nao ...
    Type: ORIGINAL ARTICLE
    Subject area: Antithrombotic Therapy
    2021 Volume 85 Issue 6 Pages 808-816
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: January 08, 2021
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    Supplementary material

    Background:The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).

    Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y12reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009).

    Conclusions:In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

  • Jihoon Kim, Young Bin Song, Ju-Hyeon Oh, Deok-Kyu Cho, Jin Bae Lee, Sa ...
    Type: ORIGINAL ARTICLE
    Subject area: Antithrombotic Therapy
    2021 Volume 85 Issue 6 Pages 817-825
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: January 09, 2021
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    Supplementary material

    Background:The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI).

    Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12–0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02–1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2–5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03–4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08–5.17; P=0.031; Pinteraction=0.885) patients.

    Conclusions:Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.

Coronary Intervention
  • Shigeru Saito, Seiji Yamazaki, Akihiko Takahashi, Atsuo Namiki, Tomohi ...
    Type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 6 Pages 826-833
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: February 05, 2021
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    Supplementary material

    Background:Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhance vessel compliance and optimize stent deployment. The objective of this study was to assess the safety and effectiveness of IVL treatment of de novo stenoses involving severely calcified coronary vessels in a Japanese population.

    Methods and Results:Disrupt CAD IV (NCT04151628) was a prospective, multicenter study designed for Japanese regulatory approval of coronary IVL (SWM-1234). The primary safety endpoint was freedom from major adverse cardiac events (MACE) at 30 days. The primary effectiveness endpoint was procedural success (residual stenosis <50% by QCA without in-hospital MACE). Noninferiority analyses for the primary endpoints were performed by comparing the CAD IV cohort with a propensity-matched historical IVL control group. Patients (intent-to-treat, n=64) were enrolled from 8 centers in Japan. Severe calcification by core laboratory assessment was present in all lesions, with a calcified length of 49.8±15.5 mm and a calcium angle of 257.9±78.4° by optical coherence tomography. Primary endpoints were achieved with non-inferiority demonstrated for freedom from 30-day MACE (CAD IV: 93.8% vs. Control: 91.2%, P=0.008), and procedural success (CAD IV: 93.8% vs. Control: 91.6%, P=0.007). No perforations, abrupt closures, or slow/no-reflow events occurred at any time during the procedures.

    Conclusions:Coronary IVL demonstrated high procedural success with low MACE rates in severely calcified lesions in a Japanese population.

  • Kenichi Sakakura
    Type: EDITORIAL
    2021 Volume 85 Issue 6 Pages 834-836
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: February 11, 2021
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  • Kenji Kanenawa, Kyohei Yamaji, Takashi Morinaga, Takashi Hiromasa, Mas ...
    Type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 6 Pages 837-846
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: February 26, 2021
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    Supplementary material

    Background:The aim of this study is to evaluate clinical outcomes after percutaneous coronary intervention (PCI) in patients with cancer.

    Methods and Results:Cancer screening was recommended before PCI in consecutive 1,303 patients who underwent their first PCI. By using cancer screening, cancer was diagnosed in 29 patients (2.2%). In total, 185 patients had present or a history of cancer. Patients with cancer more often suffered from non-cardiac death than those without (4.4% vs. 1.5%, P=0.006), and patients with cancer requiring ongoing therapy (n=18) more often suffered from major bleeding compared with those with recently (≤12 months) diagnosed cancer who do not have ongoing therapy (n=59) (16.7% vs. 3.4%, P=0.049). During the 1-year follow up, 25 patients (2.0%) were diagnosed as having cancer, in which 48.0% of bleeding events led to a cancer diagnosis. Patients with high bleeding risk according to the Academic Research Consortium for high bleeding risk (ARC-HBR) were associated with a greater 1-year major bleeding risk than those without high bleeding risk in patients with (7.9% vs. 0.0%, P=0.02) and without cancer (7.1% vs. 2.5%, P<0.001), respectively.

    Conclusions:Cancer was diagnosed in 2.2% of 1,303 unselected patients before PCI by cancer screening and in 2.0% within 1-year after PCI. Cancer was associated with a greater risk of non-cardiac death, whereas ongoing active cancer was associated with greater risk of major bleeding. ARC-HBR criteria successfully identified high-bleeding risk patients, irrespective of the presence or absence of cancer.

  • Yasuko K. Bando
    Type: EDITORIAL
    2021 Volume 85 Issue 6 Pages 847-849
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: April 08, 2021
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  • Keisuke Hakamada, Genichi Sakaguchi, Akira Marui, Yoshio Arai, Atsushi ...
    Type: ORIGINAL ARTICLE
    Subject area: Coronary Intervention
    2021 Volume 85 Issue 6 Pages 850-856
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: December 19, 2020
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    Background:The effect of multiple prior percutaneous coronary interventions (PCIs) before subsequent coronary artery bypass grafting (CABG) on long-term outcomes has not been well elucidated.

    Methods and Results:Between 2007 and 2016, 1,154 patients undergoing primary isolated CABG in our institution had no prior PCI (Group N), 225 had a single prior PCI (Group S), and 272 had multiple prior PCIs (Group M). Cumulative incidences of all-cause death, cardiac death and myocardial infarction (MI) at 10 years post-CABG were highest in Group M. After adjusting for confounders, the risk of all-cause death was higher in Group M than in Group N (hazard ratio [HR] 1.45; 95% confidence interval [CI], 1.10–1.91; P<0.01). Between Groups N and S, however, the risk of all-cause death was not different. The risks of cardiac death and MI were likewise higher in Group M than in Group N (HR, 2.39; 95% CI, 1.55–3.71; P<0.01 and HR, 3.65; 95% CI, 1.16–11.5; P=0.03, respectively), but not different between Groups N and S. The risk of repeat revascularization was not different among any of the groups.

    Conclusions:Multiple prior PCIs was associated with higher risks of long-term death and cardiovascular events. The incidence of repeat revascularization after CABG was low regardless of the history of single/multiple PCIs.

Imaging
  • Atsushi Kyodo, Makoto Watanabe, Akihiko Okamura, Saki Iwai, Azusa Saka ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 6 Pages 857-866
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: January 27, 2021
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    Supplementary material

    Background:The association between unfavorable post-stent optical coherence tomography (OCT) findings and subsequent stent thrombosis (ST) remains unclear. This study investigated the ST-related characteristics of post-stent OCT findings at index percutaneous coronary intervention (PCI).

    Methods and Results:Fifteen patients with ST onset after OCT-guided PCI (ST group) were retrospectively enrolled. Post-stent OCT findings in the ST group were compared with those in 70 consecutive patients (reference group) without acute coronary syndrome onset for at least 5 years after OCT-guided PCI. The incidence of acute myocardial infarction (AMI) was higher in the ST than reference group (60.0% vs. 17.1%, respectively; P=0.0005). The incidence of incomplete stent apposition (93.3% vs. 55.7%; P=0.0064), irregular protrusion (IP; 93.3% vs. 62.8%; P=0.0214), and thrombus (93.3% vs. 51.4%; P=0.0028) was significantly higher in the ST than reference group. The maximum median (interquartile range) IP arc was significantly larger in the ST than reference group (265° [217°–360°] vs. 128° [81.4°–212°], respectively; P<0.0001). In AMI patients, the incidence of a maximum IP arc >180° was significantly higher in the ST than reference group (100% vs. 58.3%, respectively; P=0.0265).

    Conclusions:IP with a large arc was a significant feature on post-stent OCT in patients with ST.

  • Brunon Tomasiewicz, Piotr Kubler, Wojciech Zimoch, Michał Kosowski, Wo ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 6 Pages 867-876
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: April 22, 2021
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    Background:The aim of the study was to assess anatomical and procedural predictors of clinical and procedural failure of rotational atherectomy (RA) in an all-comers population.

    Methods and Results:A total of 534 consecutive patients who underwent RA were included in a double-center observational study. The primary composite endpoint consisted of: rota-wire introduction failure, burr-passage failure, periprocedural complications and procedure-related major adverse events. The second primary endpoint included rota-wire introduction failure and burr-passage failure. The primary endpoint occurred in 76 (14.2%) patients and the second primary endpoint occurred in 64 (12%) Periprocedural complications occurred in 23 (4.3%) and procedure-related adverse events in 23 (4.3%) patients. Multivariable analysis revealed angulation on lesion ≤90° (HR=2.18, 95% CI: 1.21–3.94, P=0.0096) and sequential lesion (HR=1.89, 95% CI: 1.01–3.54, P=0.046) as independent predictors of no clinical success of RA. Multivariable analysis revealed again that angulation on lesion ≤90° (HR=2.26, 95% CI: 1.16–4.40, P=0.02) and sequential lesion (HR=3.77, 95% CI: 1.64–8.69, P<0.01) as independent predictors of no procedural success of RA.

    Conclusions:The presence of an acute angulation on lesion and sequential lesion are independent determinants of clinical and procedural failure of RA. Further research is necessary to establish a score predicting RA failure, which can help in preproceduralrisk stratification of patients undergoing complex percutaneous coronary intervention with RA.

  • Yasuyuki Suzuki, Naoya Matsumoto, Sakura Nagumo, Rei Matsuo, Keiichiro ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 6 Pages 877-882
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: January 28, 2021
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    Background:The incremental predictive value of the coronary artery calcium score (CACS) for risk stratification of coronary revascularization in patients with normal or mildly abnormal nuclear myocardial perfusion single photon emission computed tomography (MPS) scores is unknown.

    Methods and Results:We analyzed 528 patients in whom CACS was calculated and who underwent stress MPS within 3 months. Patients with known coronary artery disease, prior coronary revascularization, and those undergoing hemodialysis were excluded. Patients were followed-up with coronary revascularization based on the evidence of physiological ischemia defined by fractional flow reserve or severe coronary stenosis (≥90%). CACS was significantly associated with the summed stress score (SSS) from MPS assessment. Multivariate logistic regression analysis showed that high CACS (≥300; odds ratio [OR] 5.44, 95% confidence interval [CI] 2.28–13.0) and SSS (OR 1.29, 95% CI 1.18–1.40) were significant (P<0.001) predictors of future coronary revascularization. The log-rank test showed that high CACS stratified coronary revascularization in normal SSS (0–3; P<0.001) or mildly abnormal SSS (4–8; P=0.028) groups, whereas high CACS did not significantly stratify coronary revascularization in moderate to severe SSS (≥9; P=0.757).

    Conclusions:Risk stratification using CACS with a cut-off value 300 may have incremental predictive value for revascularization in patients with normal or mildly abnormal MPS.

  • Hirohiko Ando, Yusuke Nakano, Hiroaki Sawada, Hirofumi Ohashi, Hiroaki ...
    Type: ORIGINAL ARTICLE
    Subject area: Imaging
    2021 Volume 85 Issue 6 Pages 883-890
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: February 05, 2021
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    Supplementary material

    Background:High-resolution intravascular ultrasound (HR-IVUS) is the most recently developed IVUS technology, which allows the detailed assessment of intravascular structures. The aim of this study was to evaluate the diagnostic performance of HR-IVUS in the detection of abnormal post-stent findings.

    Methods and Results:Patients with acute coronary syndrome underwent both HR-IVUS and optical coherence tomography (OCT) for post-stent evaluations. Quantitative measurements for stented segments and qualitative assessments for abnormal post-stent findings (stent edge dissection, intrastent tissue protrusion, and incomplete stent apposition [ISA]) were performed. Forty-seven patients underwent both HR-IVUS and OCT after stent implantation. HR-IVUS identified a larger minimal lumen area and a larger minimal lumen diameter than OCT (6.66±1.98 mm2vs. 5.61±1.79 mm2and 2.87±0.42 mm vs. 2.63±0.43 mm, respectively; both P<0.001). The sensitivity of HR-IVUS for the identification of stent edge dissection, intrastent tissue protrusion, and ISA were 20.0%, 48.9%, and 27.2%, respectively.

    Conclusions:In terms of post-stent evaluation, the diagnostic performance of HR-IVUS remains insufficient. Abnormal post-stent findings might be underestimated when performing HR-IVUS due to its low sensitivity.

Population Science
  • Hayato Tada, Hirofumi Okada, Akihiro Nomura, Soichiro Usui, Kenji Saka ...
    Type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 6 Pages 891-897
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: December 03, 2020
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    Supplementary material

    Background:This study is aimed to compare the efficacy of the 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria, which focuses on only 3 essential clinical manifestations, with that of Dutch Lipid Clinic Network (DLCN) FH criteria, which adopts a scoring system of multiple elements.

    Methods and Results:A total of 680 Japanese dyslipidemic participants (51% men) were enrolled between 2006 and 2018, all of whom had full evaluations of low-density lipoprotein (LDL) cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes (LDLR,APOB, andPCSK9). Predictive values for the existence of FH mutations by both clinical criteria were evaluated. Overall, 173 FH patients were clinically diagnosed by using the 2017 JAS criteria and 100, 57, 156, and 367 subjects were also diagnosed as having definite, probable, possible, and unlikely FH by the DLCN FH criteria, respectively. The positive and negative likelihood ratio predicting the presence of FH mutations by using the 2017 JAS FH criteria were 19.8 and 0.143, respectively; whereas, using the DLCN criteria of definite, probable, and possible FH, the ratios were 29.2 and 0.489, 9.70 and 0.332, and 3.43 and 0.040, respectively.

    Conclusions:Among Japanese patients, the JAS 2017 FH criteria is considered superior to diagnose FH mutation-positive patients and simultaneously rule out FH mutation-negative patients compared with the DLCN FH criteria.

  • Mariko Harada-Shiba
    Type: EDITORIAL
    2021 Volume 85 Issue 6 Pages 898-899
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: March 24, 2021
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  • Chan-Won Kim, Sungwoo Hong, Yoosoo Chang, Jung Ah Lee, Hocheol Shin, S ...
    Type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 6 Pages 900-907
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: December 11, 2020
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    Supplementary material

    Background:A high level of apolipoprotein B (apoB) is associated with incident coronary artery disease (CAD) when low-density lipoprotein cholesterol (LDL-C) level is discordantly low or concordantly high. However, data on the relationship of apoB with subclinical measure of CAD are limited.

    Methods and Results:A total of 14,205 men (mean age 41.0 years) who were free of cardiovascular disease at baseline and who underwent a health checkup exam, including measurement of coronary artery calcium (CAC), were studied. Of the study group, 2,773 participants (19.5%) had CAC at baseline, and CAC progression was observed in 2,550 (18.0%). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing discordantly high apoB/low LDL-C and concordantly high apoB/high LDL-C with concordantly low apoB/low LDL-C were 1.51 (0.98–2.32) and 2.70 (2.19–3.33), respectively. The corresponding relative risks for CAC progression were 1.26 (1.02–1.56) and 1.49 (1.34–1.66), respectively. These associations did not change appreciably after adjustment for insulin resistance and subclinical inflammation.

    Conclusions:Discordant analysis showed that a high apoB level was strongly associated with prevalence and progression of CAC independent of LDL-C in a large cohort of healthy adults. The present study results highlighted the importance of an apoB measure as a potential target for primary prevention of coronary atherosclerosis in healthy adults.

  • Yukiko Okami, Hirotsugu Ueshima, Yasuyuki Nakamura, Keiko Kondo, Aya K ...
    Type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 6 Pages 908-913
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: December 10, 2020
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    Supplementary material

    Background:This study assessed sex-specific time-associated changes in the impact of risk factors on coronary artery disease (CAD) mortality in a general population over long-term follow-up.

    Methods and Results:A prospective longitudinal cohort study was conducted on representative Japanese populations followed up for 29 years. Data from 8,396 participants (3,745 men, 4,651 women) were analyzed. The sex-specific multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 4 risk factors (smoking, diabetes, serum total cholesterol [TC], and systolic blood pressure [SBP]) for CAD mortality were calculated at baseline and at 10, 15, 20, 25, and 29 years of follow-up. In men, smoking (HR 3.23; 95% CI 1.16–9.02) and a 1-SD increase in TC (HR 1.82; 95% CI 1.29–2.57) were strongly associated with a higher risk of CAD in the first 10 years, but this association decreased over time. Diabetes (HR 2.30; 95% CI 1.37–3.85) and a 1-SD increase in SBP (HR 1.23; 95% CI 1.00–1.50) were strongly correlated with a higher risk of CAD after 29 years). In women, diabetes was correlated with CAD after 20 years (HR 2.53; 95% CI 1.19–5.36) and this correlation persisted until after 29 years (HR 2.47; 95% CI 1.40–4.35).

    Conclusions:The duration of follow-up needed for the accurate assessment of risk factors for CAD mortality varies according to risk factor and sex.

  • Hidetaka Itoh, Hidehiro Kaneko, Hiroyuki Kiriyama, Tatsuya Kamon, Kats ...
    Type: ORIGINAL ARTICLE
    Subject area: Population Science
    2021 Volume 85 Issue 6 Pages 914-920
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: February 05, 2021
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    Background:Obesity and metabolic disorders frequently coexist, and both are established risk factors for cardiovascular disease (CVD). Although the phenotype of obesity without metabolic disorders, referred to as metabolically healthy obesity (MHO), is attracting clinical interest, the pathophysiological impact of MHO remains unclear.

    Methods and Results:Using the Japan Medical Data Center database, we studied 802,288 subjects aged ≥20 years without any metabolic disorders or a prior history of CVD. MHO, defined as obesity (body mass index ≥25 kg/m2) with no metabolic disorders, was observed in 9.8% of the study population. The subjects’ mean (±SD) age was 42.8±9.4 years and 44.7% were men. The mean follow-up period was 1,126±849 days. Multivariable Cox regression analysis showed that MHO alone did not significantly increase the risk of any CVD. However, abdominal obesity alone increased the risk of heart failure and atrial fibrillation. Moreover, the coexistence of MHO and abdominal obesity increased the risk of myocardial infarction, angina pectoris, heart failure, and atrial fibrillation. The incidence of stroke was not associated with the presence of MHO and abdominal obesity.

    Conclusions:Among individuals with no metabolic disorders, MHO alone did not significantly increase the subsequent CVD risk. However, individuals with comorbid MHO and abdominal obesity had a higher risk of myocardial infarction, angina pectoris, heart failure, and atrial fibrillation, suggesting the prognostic importance of abdominal obesity in subjects with MHO.

COVID-19
  • Shingo Matsumoto, Shunsuke Kuroda, Takahide Sano, Takeshi Kitai, Taish ...
    Type: ORIGINAL ARTICLE
    Subject area: COVID-19
    2021 Volume 85 Issue 6 Pages 921-928
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: April 29, 2021
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    Supplementary material

    Background:This study investigated the effects of age on the outcomes of coronavirus disease 2019 (COVID-19) and on cardiac biomarker profiles, especially in patients with cardiovascular diseases and/or risk factors (CVDRF).

    Methods and Results:A nationwide multicenter retrospective study included 1,518 patients with COVID-19. Of these patients, 693 with underlying CVDRF were analyzed; patients were divided into age groups (<55, 55–64, 65–79, and ≥80 years) and in-hospital mortality and age-specific clinical and cardiac biomarker profiles on admission evaluated. Overall, the mean age of patients was 68 years, 449 (64.8%) were male, and 693 (45.7%) had underlying CVDRF. Elderly (≥80 years) patients had a significantly higher risk of in-hospital mortality regardless of concomitant CVDRF than younger patients (P<0.001). Typical characteristics related to COVID-19, including symptoms and abnormal findings on baseline chest X-ray and computed tomography scans, were significantly less prevalent in the elderly group than in the younger groups. However, a significantly (P<0.001) higher proportion of elderly patients were positive for cardiac troponin (cTn), and B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP) levels on admission were significantly higher among elderly than younger patients (P<0.001 and P=0.001, respectively).

    Conclusions:Elderly patients with COVID-19 had a higher risk of mortality during the hospital course, regardless of their history of CVDRF, were more likely to be cTn positive, and had significantly higher BNP/NT-proBNP levels than younger patients.

Basic Science
  • Shinichi Goto, Genki Ichihara, Yoshinori Katsumata, Seien Ko, Atsushi ...
    Type: ORIGINAL ARTICLE
    Subject area: Basic Science
    2021 Volume 85 Issue 6 Pages 929-938
    Published: May 25, 2021
    Released: May 25, 2021
    [Advance publication] Released: March 03, 2021
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    Supplementary material

    Background:Timely differentiation of monocytes into M2-like macrophages is important in the cardiac healing process after myocardial infarction (MI), but molecular mechanisms governing M2-like macrophage differentiation at the transcriptional level after MI have not been fully understood.

    Methods and Results:A time-series microarray analysis of mRNAs and microRNAs in macrophages isolated from the infarcted myocardium was performed to identify the microRNAs involved in regulating the process of differentiation to M2-like macrophages. Correlation analysis revealed 7 microRNAs showing negative correlations with the progression of polarity changes towards M2-like subsets. Next, correlation coefficients for the changes in expression of mRNAs and miRNAs over time were calculated for all combinations. As a result, miR-27a-5p was extracted as a possible regulator of the largest number of genes in the pathway for the M2-like polarization. By selecting mouse mRNAs and human mRNAs possessing target sequences of miR-27a-5p and showing expression patterns inversely correlated with that of miR-27a-5p, 8 potential targets of miR-27a-5p were identified, includingPpm1l. Using the mouse bone marrow-derived macrophages undergoing differentiation into M2-like subsets by interleukin 4 stimulation, we confirmed that miR-27a-5p suppressed M2-related genes by negatively regulatingPpm1lexpression.

    Conclusions:Ppm1land miR-27a-5p may be the key molecules regulating M2-like polarization, with miR-27a-5p inhibiting the M2-like polarization through downregulation ofPpm1lexpression.

Rapid Communications
Images in Cardiovascular Medicine
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