Serum uric acid (UA) is taken up by endothelial cells and reduces the level of nitric oxide (NO) by inhibiting its production and accelerating its degradation. Cytosolic and plasma xanthine oxidase (XO) generates superoxide and also decreases the NO level. Thus, hyperuricemia is associated with impaired endothelial function. Hyperuricemia is often associated with vascular diseases such as chronic kidney disease (CKD) and cardiovascular disease (CVD). It has long been debated whether hyperuricemia is causally related to the development of these diseases. The 2020 American College of Rheumatology Guideline for the Management of Gout (ACR2020) does not recommend pharmacological treatment of hyperuricemia in patients with CKD/CVD. In contrast, the Japanese Guideline on Management of Hyperuricemia and Gout (JGMHG), 3rdedition, recommends pharmacological treatment of hyperuricemia in patients with CKD. In a FREED study on Japanese hyperuricemic patients with CVD, an XO inhibitor, febuxostat, improved the primary composite endpoint of cerebro-cardio-renovascular events, providing a rationale for the use of urate-lowering agents (ULAs). Since a CARES study on American gout patients with CVD treated with febuxostat revealed increased mortality, ACR2020 recommends switching to different ULAs. However, there was no difference in the mortality of Japanese patients between the febuxostat-treated group and the placebo or allopurinol-treated groups in either the FEATHER or FREED studies.
Background:Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).
Methods and Results:This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000–1.011, P=0.029).
Conclusions:The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.
Background:Data on the association of baseline thrombocytopenia (TP) with long-term outcomes of patients with acute ST-segment elevated myocardial infarction (STEMI) are still limited.
Methods and Results:A total of 16,957 consecutive cases of patients with STEMI from multiple centers that participated in the China Acute Myocardial Infarction (CAMI) registry were included in this study. Two-year clinical outcomes were evaluated between patients with TP and those with a normal platelet count (PLT). Cases coexisting with baseline TP accounted for 2.1%. The rates of 2-year all-cause death (21.4% and 11.4%, P<0.001) and major adverse cardiovascular and cerebrovascular events (MACCE) (23.6% and 13.9%, P<0.001) were significantly higher in cases with TP, compared with the normal PLT group. After multivariate adjustment, compared with the control, cases with TP were not independently associated with 2-year all-cause death (HR: 1.21; 95% CI: 0.96–1.52; P=0.110) and MACCE (HR: 1.18; 95% CI: 0.95–1.47; P=0.132). After propensity score matching (PSM), the rates of 2-year all-cause death and MACCE were similar between the 2 groups (20.7% and 17.9%, P=0.317; 23.0% and 19.9%, P=0.288). Multivariable adjustment after PSM showed baseline TP was not independently associated with all-cause death (HR: 1.21; 95% CI: 0.88–1.67; P=0.240) and MACCE (HR: 1.21; 95% CI: 0.89–1.63; P=0.226).
Conclusions:Patients with STEMI and baseline TP had higher rates of all-cause death and MACCE; however, baseline TP was not independently associated with 2-year adverse outcomes in patients with STEMI after multivariate adjustment and controlling for baseline differences.
Background:This observational study validated Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria and the Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention.
Methods and Results:Risk clusters of 939 STEMI patients with traceable 1-year outcomes were assessed according to ARC-HBR criteria and PRECISE-DAPT score. The diagnostic accuracy and first-year probability of bleeding events, defined as Bleeding Academic Research Consortium (BARC) 3 or 5, according to risk cluster were assessed. Of all patients, 42.9% and 46.8% were classified as HBR (ARC-HBR criteria) and at high risk (PRECISE-DAPT score), respectively, and bleeding events were observed in 13.7% and 16.2% of these patients. The C-statistic for ARC-HBR criteria and the PRECISEDAPT score was 0.60 and 0.69, respectively (P<0.01). Patients with mechanical hemodynamic support devices had high bleeding rates, even in the non-HBR group (22.6%), and excluding these patients improved the C-statistics, making them equivalent between the 2 models (0.72 vs. 0.74; P=0.53). Bleeding event probabilities (95% confidence intervals) were equivalent in high-risk patients in the 2 models (0.12 [0.09–0.16] vs. 0.12 [0.08–0.16]).
Conclusions:After exclusion of patients with mechanical devices, who had high bleeding event rates regardless of risk cluster, both ARC-HBR criteria and the PRECISE-DAPT score had high predictive ability.
Background:Studies investigating the modulators of mortality benefit conferred by peri-angioplasty glycoprotein IIb/IIIa inhibitors in ST-elevation myocardial infarction (STEMI) are still lacking.
Methods and Results:A prospective database (n=1,025) of consecutive cases undergoing primary percutaneous coronary intervention for STEMI was retrospectively analyzed. For patients in Killip class I, II or III, IV, the multivariate-adjusted hazard ratios of 30-day all-cause mortality associated with adjunctive tirofiban were 3.873 (95% CI 0.504–29.745; P=0.193), 0.550 (95% CI 0.188–1.609; P=0.275), and 0.264 (95% CI 0.099–0.704; P=0.008), respectively. The P value for a linear trend was 0.032. Patients who had a body mass index (BMI) within 22.9–25.0 kg/m2had a significant benefit from tirofiban (adjusted HR 0.344; 95% CI 0.145–0.814; P=0.015) compared to other BMI groups. The P value for a quadratic trend was 0.012. A novel Killip−BMI score (KBS = 2.5 × Killip category − | BMI − 24 |) was calculated to select the beneficial population. A KBS ≥2 was associated with significant mortality benefit, whereas a KBS <0 predicted increased 30-day mortality with tirofiban use.
Conclusions:Survival benefit from peri-angioplasty tirofiban therapy for STEMI was positively correlated with the Killip class. Tirofiban should be used cautiously in either underweight or overweight patients. The novel KBS used in this study can guide peri-angioplasty use of adjunctive tirofiban in patients with STEMI undergoing primary angioplasty.
Background:In developed countries, the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) has outpaced that of ST-segment elevation myocardial infarction (STEMI). However, whether this trend is observed in Japan, in which the aging of society is rapidly progressing, remains to be elucidated.
Methods and Results:This study retrospectively investigated the trends over time in the incidence of acute coronary syndrome (ACS) between August 2009 and July 2019 at 2 institutions in Izumo City (in rural Japan), which has an elderly population. Crude and age-sex-adjusted incidences of total ACS, STEMI, and non-ST-segment elevation-ACS (NSTE-ACS; including NSTEMI and unstable angina pectoris) were calculated for each year. In the total population, factors associated with the development of NSTEMI were evaluated by multivariate analysis. In total, 1,087 patients were enrolled. The age-adjusted incidence of NSTE-ACS in male patients aged ≥75 years showed a significantly increasing trend. The proportion of NSTEMI per total ACS cases showed a significantly increasing trend over the entire study period. In the multivariate analysis, pre-development use of ≥3 medications for comorbidities was associated with the development of NSTEMI, independent of high-sensitivity cardiac troponin assay use.
Conclusions:This study demonstrated an increasing trend in the incidence of NSTEMI in a rural high-aged Japanese population. In addition to the widespread use of high-sensitivity cardiac troponin assays, early medication use for comorbidities might have contributed to this trend.
Background:The optimal percutaneous coronary intervention (PCI) strategy for multivessel lesions in the setting of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains controversial. This study sought to compare long-term prognosis between single-vessel PCI (SV-PCI) and multivessel PCI (MV-PCI) in patients with multivessel coronary artery disease (MV-CAD) presenting with NSTE-ACS in a real-world population.
Methods and Results:NSTE-ACS patients with MV-CAD undergoing PCI in Fuwai Hospital in 2013 were consecutively enrolled. SV-PCI was defined as targeting only the culprit vessel, whereas MV-PCI was defined as treating ≥1 coronary artery(s) in addition to the culprit vessel at the index procedure. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at 2 years, consisting of all-cause death, cardiac death, myocardial infarction, unplanned revascularization, or stroke. A total of 3,338 patients were included. Both SV-PCI and MV-PCI were performed in 2,259 patients and 1,079 patients, respectively. During a median follow up of 2.1 years, the MACCE rates and adjusted risk were not significantly different between the SV-PCI and MV-PCI groups (13.1% vs. 14.0%, P=0.735; adjusted HR=0.967, 95% CI: 0.792–1.180). Similar results were observed in propensity-score matching and inverse probability of treatment weighting analyses. Subgroup analysis revealed a consistent effect on 2-year MACCE across different subgroups.
Conclusions:In NSTE-ACS patients with MV-CAD, MV-PCI is not superior to SV-PCI in terms of long-term MACCE.
Background:Rheumatoid arthritis (RA) has extra-articular manifestations of cardiovascular diseases and is associated with a high mortality rate in Western populations. This study aimed to investigate the risk of acute coronary syndrome (ACS) and atrial fibrillation (AF) associated with RA in a Korean population.
Methods and Results:Patients were selected from a senior cohort from the Korean National Health Insurance Service in 2002, and followed until 31 December 2015. Patients with newly developed ACS and AF were identified and compared with controls for a 10-year period using time-dependent propensity and risk-set matching. A total of 4,217 incident RA patients and their 8,432 controls comprised the incident RA and matched cohorts, respectively. ACS was identified during 24,642 person-years [incidence rate (IR) 402 per 10,000 person-years, 95% confidence interval (CI) 330–489] among the RA cohort. In the matched cohort, 141 ACS patients were identified during 50,011 person-years (IR 282 per 100,000 person-years, 95% CI 239–333). RA patients were 1.43-fold more likely to develop ACS than the matched controls [hazard ratio (HR) 1.43, 95% CI 1.10–1.84], but showed similar occurrence risk of AF (HR 1.06, 95% CI 0.83–1.35).
Conclusions:A higher risk for ACS and a similar risk for AF were found by risk-set matched analysis in a senior RA cohort compared with the control, using Korean nationwide long-term data.
Background:In Japan there is no consensus on how to efficiently measure quality indicators (QIs), defined as a standard of care, for acute ischemic stroke (AIS). Using information from a health insurance claims database and electronic medical records, we evaluated the feasibility and validity of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (IV rt-PA) or endovascular therapy (EVT).
Methods and Results:AIS patients receiving rt-PA or EVT between 2013 and 2015 were identified. We selected 17 AIS QI measures for primary stroke centers (PSCs) and 8 for comprehensive stroke centers (CSCs). Defined QIs were calculated for each hospital and then averaged. In total, the data of 8,206 patients (rt-PA 83.7%, EVT 34.9%) from 172 hospitals were obtained. Median National Institute of Health Stroke Scale score at admission was 14, and 37.7% of the patients were functionally independent at discharge. All target QIs were successfully measured with fewer missing values, and the accuracy of preset data was about 90%. Adherence rates were low (<50%) in 5 QI measures among PSCs, including door-to-needle time ≤1 h, and in 1 QI measure among CSCs (door-to-brain and vascular imaging time ≤30 min).
Conclusions:Measuring QIs for AIS by this novel approach was feasible and reliable in the provision of a national benchmark.
Background:This study explored the value of cystatin C (CysC) in predicting stroke recurrence in patients with acute ischemic stroke.
Methods and Results:This was a post hoc analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) on 3,474 acute ischemic stroke patients with documented serum CysC and high-sensitivity C-reactive protein (hsCRP) concentrations. Study outcomes included stroke recurrence and combined vascular events within 2 years after stroke. In stroke patients with higher (i.e., ≥4.8ng/mL), but not lower, hsCRP concentrations, a higher CysC concentration (i.e., ≥0.78 mg/L) was associated with a 2.48-fold increase in the risk of recurrent stroke (95% confidence interval [CI] 1.37–4.51; P=0.003) and a 2.04-fold increase in the risk of vascular events (95% CI 1.27–3.28; P=0.003). Serum hsCRP concentrations significantly modified the association of serum CysC with recurrent stroke (Pinteraction=0.001) and vascular events (Pinteraction=0.007). Moreover, CysC may improve reclassification of stroke recurrence (net reclassification improvement [NRI] 42.9%, P=0.001; integrated discrimination improvement [IDI] 1.2%, P=0.001) and vascular events (NRI 35.8%, P=0.001; IDI 1.1%, P=0.004).
Conclusions:In ischemic stroke patients with high hsCRP concentrations, higher CysC concentrations increased the risk of stroke recurrence and vascular events. This indicates that the predictive value of CysC on stroke recurrence may depend on the inflammation status of patients.