Cardiovascular Events In Japanese Patients Research Articles

Cut-off values of Geriatric Nutritional Risk Index for cardiovascular events in Japanese patients with acute myocardial infarction.

The Geriatric Nutritional Risk Index (GNRI) is a straightforward nutritional risk assessment tool with an established relationship with poor prognosis in patients with heart failure. However, the utility of the GNRI in patients with acute myocardial infarction (AMI) remains unclear given the time-dependent changes in the pathophysiology of AMI and the selected endpoints. Accordingly, we aimed to evaluate the optimal cut-off values of the GNRI for cardiovascular events in patients with AMI. We used time-dependent receiver operating characteristic analysis to identify the optimal cut-off values for two endpoints, all-cause death and major adverse cardiac events (MACE: all-cause death, non-fatal myocardial infarction, hospitalization for heart failure, and stroke), over 4years in 360 patients with AMI between 2012 and 2020. The cumulative incidence of MACE was 11.6%. The cut-off value of the GNRI for all-cause death was 82.7 (area under the curve [AUC], 0.834) at 3months and 90.3 (AUC 0.854) at 4years. The cut-off value of the GNRI for MACE was 83.0 (AUC 0.841) at 3months and 95.3 (AUC 0.821) at 4years. The GNRI demonstrated consistently high reliability relative to other indicators of AMI. Our findings indicated that the optimal cut-off value and reliability of the GNRI for cardiovascular events varied according to the endpoints and observation periods. GNRI emerges as a crucial predictor of prognosis for patients with AMI.

Influenza Vaccination and Cardiovascular Events in Japanese Patients With Heart Failure - Findings From the PARALLEL-HF Trial.

Influenza is associated with an increased risk for cardiovascular events in patients with heart failure (HF). This study aimed to investigate the prevalence of influenza vaccination among Japanese patients with HF enrolled in the PARALLEL-HF (Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) trial and the association between receiving influenza vaccination and cardiovascular events including death or HF hospitalization. In PARALLEL-HF, in which 223 patients with HF and reduced ejection fraction (HFrEF) were randomized to the angiotensin-receptor neprilysin inhibitor (sacubitril/valsartan) or enalapril, 97 (43%) received influenza vaccination. Influenza vaccination tended to be associated, though statistically not significant, with a lower risk for all-cause death (adjusted hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.32-1.39) and cardiopulmonary or influenza-related hospitalization or death (adjusted HR: 0.72; 95% CI: 0.46-1.11) in propensity score-adjusted models. The influenza vaccination rate in Japanese patients with HFrEF who were well managed on guideline-directed medical therapy was suboptimal despite recommendations from clinical practice guidelines. However, importantly, it could be associated with better clinical benefits.

The associations of accumulative LDL-C with Achilles tendon thickening and major adverse cardiovascular events in Japanese patients with familial hypercholesterolemia

The associations of accumulative LDL-C with Achilles tendon thickening and major adverse cardiovascular events in Japanese patients with familial hypercholesterolemia

Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166 <pmol/L, hazard ratio in Q4: 1.74, [95% CI, 1.04-2.93]). Monitoring ANGPTL8 levels over time might be useful to assess residual risk of cardiovascular secondary events in patients with cardiovascular disease undergoing statin therapy.

Mean annual intradialytic blood pressure decline and cardiovascular events in Japanese patients on maintenance hemodialysis.

An intradialytic systolic blood pressure (SBP) decline, which defines intradialytic hypotension, may be associated with higher all-cause mortality. However, in Japanese patients on hemodialysis (HD), the association between intradialytic SBP decline and patient outcomes is unclear. This retrospective cohort study included 307 Japanese patients undergoing HD over 1 year in three dialysis clinics and evaluated the association between the mean annual intradialytic SBP decline (predialysis SBP-nadir intradialytic SBP) and clinical outcomes, including major adverse cardiovascular events (MACEs; cardiovascular death, nonfatal myocardial infarction or unstable angina, stroke, heart failure, and other severe cardiovascular events requiring hospitalization) by following up for 2 years. The mean annual intradialytic SBP decline was 24.2 (25-75th percentile, 18.3-35.0) mmHg. In the model fully adjusted for intradialytic SBP decline tertile group (T1, <20.4 mmHg; T2, 20.4 to <29.9 mmHg; T3, ≥29.9 mmHg), predialysis SBP, age, sex, HD vintage, Charlson comorbidity index, ultrafiltration rate, use of renin-angiotensin system inhibitors, corrected calcium, phosphorus, human atrial natriuretic peptide, geriatric nutritional risk index, normalized protein catabolism rate, C-reactive protein, hemoglobin, and use of pressor agents, Cox regression analyses showed that the hazard ratio (HR) was significantly higher for T3 than for T1 for MACEs (HR, 2.38; 95% confidence interval 1.12-5.09) and all-cause hospitalization (HR, 1.68; 95% confidence interval 1.03-2.74). Therefore, in Japanese patients on HD, a greater intradialytic SBP decline was associated with worse clinical outcomes. Further studies are warranted to investigate whether interventions to attenuate the intradialytic SBP decline will improve the prognosis of Japanese patients on HD.

Optimal target of LDL cholesterol level for statin treatment: challenges to monotonic relationship with cardiovascular events

BackgroundAggressive lipid lowering by high-dose statin treatment has been established for the secondary prevention of coronary artery disease (CAD). Regarding the low-density lipoprotein cholesterol (LDL-C) level, however, the “The lower is the better” concept has been controversial to date. We hypothesized that there is an optimal LDL-C level, i.e., a “threshold” value, below which the incidence of cardiovascular events is no longer reduced. We undertook a subanalysis of the REAL-CAD study to explore whether such an optimal target LDL-C level exists by a novel analysis procedure to verify the existence of a monotonic relationship.MethodsFor a total of 11,105 patients with CAD enrolled in the REAL-CAD study, the LDL-C level at 6 months after randomization and 5-year cardiovascular outcomes were assessed. We set the “threshold” value of the LDL-C level under which the hazards were assumed to be constant, by including an artificial covariate max (0, LDL-C − threshold) in the Cox model. The analysis was repeated with different LDL-C thresholds (every 10 mg/dl from 40 to 100 mg/dl) and the model fit was assessed by log-likelihood.ResultsFor primary outcomes such as the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization, the model fit assessed by log-likelihood was best when a threshold LDL-C value of 70 mg/dl was assumed. And in the model with a threshold LDL-C ≥ 70 mg/dl, the hazard ratio was 1.07 (95% confidence interval 1.01–1.13) as the LDL-C increased by 10 mg/dl. Therefore, the risk of cardiovascular events decreased monotonically until the LDL-C level was lowered to 70 mg/dl, but when the level was further reduced, the risk was independent of LDL-C.ConclusionsOur analysis model suggests that a “threshold” value of LDL-C might exist for the secondary prevention of cardiovascular events in Japanese patients with CAD, and this threshold might be 70 mg/dl for primary composite outcomes.Trial registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT01042730.

Association of Polypharmacy with Kidney Disease Progression in Adults with CKD.

Polypharmacy is common in patients with CKD and reportedly associated with adverse outcomes. However, its effect on kidney outcomes among patients with CKD has not been adequately elucidated. Hence, this investigation was aimed at exploring the association between polypharmacy and kidney failure requiring KRT. We retrospectively examined 1117 participants (median age, 66 years; 56% male; median eGFR, 48 ml/min per 1.73 m2) enrolled in the Fukushima CKD Cohort Study to investigate the association between the number of prescribed medications and adverse outcomes such as kidney failure, all-cause mortality, and cardiovascular events in Japanese patients with nondialysis-dependent CKD. Polypharmacy and hyperpolypharmacy were defined as the regular use of 5-9 and ≥10 medications per day, respectively. The median number of medications was eight; the prevalence of polypharmacy and hyperpolypharmacy was each 38%. During the observation period (median, 4.8 years), 120 developed kidney failure, 153 developed cardiovascular events, and 109 died. Compared with the use of fewer than five medications, adjusted hazard ratios (95% confidence intervals) associated with polypharmacy and hyperpolypharmacy were 2.28 (1.00 to 5.21) and 2.83 (1.21 to 6.66) for kidney failure, 1.60 (0.85 to 3.04) and 3.02 (1.59 to 5.74) for cardiovascular events, and 1.25 (0.62 to 2.53) and 2.80 (1.41 to 5.54) for all-cause mortality. The use of a high number of medications was associated with a high risk of kidney failure, cardiovascular events, and all-cause mortality in Japanese patients with nondialysis-dependent CKD under nephrology care.

The Influence of Eicosapentaenoic Acid to Arachidonic Acid Ratio on Long-term Cardiovascular Events Following Percutaneous Coronary Intervention.

Objective The relationship between cardiovascular disease and the serum polyunsaturated fatty acid parameters has been reported. The aim of the present study was to investigate the association between the eicosapentaenoic acid and arachidonic acid (EPA/AA) ratio and long-term cardiovascular events in patients with coronary artery disease. Methods We identified a total of 831 patients who underwent percutaneous coronary intervention and whose EPA/AA ratio was available. The patients were divided into two groups according to their serum EPA/AA ratio (median, 0.29; interquartile range 0.19-0.47): those in the lower quartile of EPA/AA ratios (Low EPA/AA group; n=231) and all other subjects (High EPA/AA group; n=600). The primary endpoints included a composite of cardiovascular death, myocardial infarction, and ischemic stroke. Results Patients in the Low EPA/AA group were significantly younger (66.0±12.6 years vs. 69.9±9.3 years, p<0.001), current smokers (33.3% vs. 22.7%, p=0.002), and had a history of myocardial infarction (20.3% vs. 12.3%, p=0.003). During the follow-up (median, 1,206 days; interquartile range, 654-1,910 days), the occurrence of the primary endpoint was significantly higher in the Low EPA/AA group than in the High EPA/AA group. Of note, the rate of cardiovascular death was significantly higher in the Low EPA/AA group, and the rates of myocardial infarction and stroke tended to be higher. Conclusion A low EPA/AA ratio was associated with long-term adverse cardiovascular events in Japanese patients with coronary artery disease.

Impact of chronic kidney disease on mid-term prognosis of stable angina patients with high-dose or low-dose pitavastatin treatment: REAL-CAD sub-study

Abstract Background We previously demonstrated that high-dose (4 mg/day) compared with low-dose (1 mg/day) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease in the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. However, little is known about whether the advantage of high-dose statins over low-dose statins is consistent among non-, mild, and moderate to severe chronic kidney disease (CKD) patients. Purpose The aim of this study was to clarify the effect of high-dose statins on cardiovascular events in Japanese patients with or without CKD. Methods The REAL-CAD study is a prospective, multicenter, randomized, open-label, blinded endpoint, physician-initiated superiority trial. In this sub-analysis of REAL-CAD study, patients were categorized into three groups according to estimated glomerular filtration rate (eGFR). Patients on hemodialysis were excluded in this study. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal ischemic stroke, or unstable angina requiring emergency hospitalization. A secondary composite endpoint was defined as a composite of the primary endpoint event or clinically-indicated coronary revascularization excluding target-lesion revascularization. Results The total population of the REAL-CAD study was 12,413 patients. After exclusion of patients lacking eGFR data, the numbers of patients categorized into non-CKD (eGFR ≥60 mL/min/1.73m2), mild CKD (eGFR; 45–60), and moderate to severe CKD (eGFR &amp;lt;45) were 7,778 (64%), 3,176 (26%), and 1,164 (10%), respectively. The median follow-up period was 3.9 years. The baseline characteristics and medications were well balanced between the two groups in each CKD group. While high-dose compared to low-dose pitavastatin significantly reduced the primary endpoint in non-CKD patients, the effect was not observed in mild CKD and moderate to severe CKD patients (Figure 1). High-dose compared with low-dose pitavastatin did not significantly reduce the secondary composite endpoint in both mild and moderate to severe CKD patients as well. High-dose pitavastatin significantly reduced the risks of MI and any coronary revascularization in non-CKD patients, however, the effects were diminished in mild CKD and moderate to severe CKD patients. There was no significant difference between high-dose and low-dose pitavastatin treatment in the risk of all-cause death, cardiovascular death, ischemic stroke, or unstable angina requiring emergency hospitalization in patients with or without CKD. Conclusion Although high-dose pitavastatin therapy significantly reduced cardiovascular events in non-CKD patients with stable angina compared to low-dose pitavastatin, such beneficial effects had diminished in Japanese patients with mild or moderate to severe CKD patients. Figure 1. Kaplan-Meier Curves for Endpoints Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Clinical Research of Lifestyle-Related Disease of the Public Health Research Foundation

P5320Reduction in high-sensitivity C-reactive protein by pitavastatin was associated with improved outcomes in Japanese patients with stable coronary artery disease: results from REAL-CAD study

Abstract Background The effect of statins on lowering high sensitivity C-reactive protein (hs-CRP) as well as low density lipoprotein cholesterol (LDL-C) has been associated with reduced risk for cardiovascular events in patients with elevated hs-CRP. However, it remains unclear whether this statin effect applies to low-risk patients with stable coronary artery disease (CAD). In this pre-specified sub-study within the REAL-CAD trial, we explored the association between achieved LDL-C/hs-CRP levels and cardiovascular events in Japanese patients with stable CAD who were treated with pitavastatin 1 mg or 4 mg/day. Methods The REAL-CAD trial randomly allocated 13,054 patients with stable CAD to pitavastatin 1 mg or 4 mg/day. LDL-C and hs-CRP were measured at baseline and at 6 months after randomization. We excluded those patients without 6-month data and those with endpoint events before 6 months (N=1915). The primary endpoint of the study was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. Outcomes were assessed by landmark analysis beyond 6 months among 4 groups that were configured based on LDL-C (median) and hs-CRP (median) targets: achieving neither target, achieving LDL-C target only, achieving hs-CRP target only, and achieving both targets. Data were adjusted for baseline characteristics including age, gender, diabetes and baseline values of LDL-C and hs-CRP. Results Median LDL-C and hs-CRP levels were 88 mg/dL and 0.52 mg/L at baseline and 80 mg/dL and 0.48 mg/L after 6 months, respectively. There was no correlation between the change in LDL-C and hs-CRP levels from baseline to 6 months (correlation coefficient: 0.009, P=0.331). Of the 11,677 patients included in the study, 25.1% (N=2799) achieved both LDL-C and hs-CRP targets, 25.3% (N=2282) met neither target, 24.8% (N=2765) met only the hs-CRP target, and 24.7% (N=2753) met only the LDL-C target. Risk of primary endpoint occurrence was significantly lower in those achieving either or both targets than in those meeting neither target (Figure A). In the subgroup analysis stratified by the randomized dose of pitavastatin, the risk for the primary endpoint was significantly lower in patients achieving both targets in both the 1mg and 4 mg arms, and in patients achieving only hs-CRP target in the 1 mg arm (Figure B, C). Figure 1 Conclusions In this subanalysis of the REAL-CAD trial, the hs-CRP lowering effect of pitavastatin was independent from LDL-C lowering. Lower achieved hs-CRP was associated with lower risk for cardiovascular events in Japanese patients with stable CAD. Acknowledgement/Funding Public Health Research Foundation, The company manufacturing the study drug (Kowa Pharmaceutical Co Ltd) was one of the entities providing financial s

Abstract 14025: Mild QTc Prolongation was Associated With Cardiovascular Events in Japanese Male Patients With Cardiovascular Risk Japan Morning Surge Home Blood Pressure (J-HOP) Study

Introduction: The relationships between QTc intervals and the risk of cardiovascular (CV) events could differ among ethnicities or between subjects with/without left ventricular hypertrophy (LVH). Hypothesis: We hypothesized that mild QTc prolongation was associated with CV events in Japanese patients with CV risk factors. Methods: Subjects were 3,592 patients enrolled in the Japan Morning Surge Home Blood Pressure Study who had one or more CV risk factors. Corrected QT intervals (QTc) were calculated using the Bazett formula. Prolonged QTc interval was defined as ≥440 ms in men and ≥460 ms in women on electrocardiogram (ECG). We divided patients into 3 subgroups according to the percentile of QTc (shortest 10%, middle 80%, and longest 10%). The primary endpoints were fatal/nonfatal CV events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection). The Sokolow-Lyon criteria (RV5(6)+SV1) ≥35 mm were used to diagnose LVH. Results: During the mean follow-up period of 48±39 months, there were 138 CV events. In male patients, those with prolonged QTc (N=57) were more likely to suffer CV events than those without prolonged QTc (N=1523) (log rank 6.22, p=0.013). A Cox proportional hazards model including age, hypertension, dyslipidemia and diabetes revealed that prolonged QTc was a significant independent predictor of CV events in male patients (hazard ratio 2.21, 95%CI 1.01-4.82, p=0.047). In female patients, CV events were similar in prolonged QTc (N=33) and non- prolonged QTc patients (N=1766, p=0.73). In male patients, the longest 10% of QTc patients (QTc≥406ms, N=157) were more likely to suffer CV events than those in the middle 80% of QTc patients (QTc 332-405ms, N=1265) and shortest 10% of QTc patients (QTc&lt;332ms, N=157) (log rank 16.57, p&lt;0.001). In the absence of LVH (N=1308), male patients in longest 10% of QTc suffered more CV events than those in the other groups (log rank 6.61, p=0.037), and in the presence of LVH (N=272), males in the longest 10% of QTc also suffered more CV events than those in the other groups (log rank 13.73, p=0.001).In female patients, CV events were similar in three subgroups. Conclusions: Mild QTc prolongation was associated with CV events in Japanese male patients with a CV risk with or without ECG-LVH.

Effects of CYP2C19 allelic variants on inhibition of platelet aggregation and major adverse cardiovascular events in Japanese patients with acute coronary syndrome: The PRASFIT-ACS study

BackgroundWe examined the effects of cytochrome P450 2C19 (CYP2C19) polymorphisms on the efficacy and safety of prasugrel and clopidogrel in a post hoc analysis of the PRASugrel compared with clopidogrel For Japanese patIenTs with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) (PRASFIT-ACS) study. MethodsJapanese ACS patients undergoing PCI were randomized (double-blind) to receive prasugrel (loading/maintenance dose: 20/3.75mg) or clopidogrel (300/75mg) plus aspirin for 24–48 weeks. Pharmacogenomic analyses were conducted in 773/1363 patients. P2Y12 reaction units (PRU) were determined using the VerifyNow® P2Y12 assay (Accumetrics, San Diego, CA, USA). CYP2C19 genotypes were classified as extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). ResultsOverall, 39.2% and 60.8% of patients in the prasugrel group and 35.2% and 64.8% of patients in the clopidogrel group were classified as EM and IM+PM, respectively. Among EM patients, PRU was significantly lower in the prasugrel group than in the clopidogrel group at 2–4 and 5–12h after the loading dose, but was similar in both groups from week 4 onwards. Among IM+PM patients, PRU was significantly lower in the prasugrel group than in the clopidogrel group throughout the study. Among EM patients, the incidence of major adverse cardiovascular events (MACE) at 24 weeks was 11.8% in the prasugrel group and 11.9% in the clopidogrel group [hazard ratio (HR): 0.99, 95% confidence interval (CI): 0.50–1.96]. Among IM+PM patients, the incidence of MACE was 9.3% in the prasugrel group and 12.5% in the clopidogrel group (HR: 0.78, 95% CI: 0.45–1.35). The incidences of major, minor, and clinically relevant bleeding were similar between the two groups for each genotype. ConclusionsPrasugrel showed more consistent antiplatelet effects than clopidogrel in Japanese ACS patients irrespective of the CYP2C19 phenotype.

Rho-associated kinase activity is an independent predictor of cardiovascular events in acute coronary syndrome.

Rho-associated kinases play an important role in a variety of cellular functions. Although Rho-associated kinase activity has been shown to be an independent predictor for future cardiovascular events in a general population, there is no information on Rho-associated kinase activity in patients with acute coronary syndrome. We evaluated leukocyte Rho-associated kinase activity by Western blot analysis in 73 patients with acute coronary syndrome and 73 age- and gender-matched control subjects. Rho-associated kinase activity within 2 hours of acute coronary syndrome onset was higher in patients with acute coronary syndrome than in the control subjects (0.95±0.55 versus 0.69±0.31; P<0.001). Rho-associated kinase activity promptly increased from 0.95±0.55 to 1.11±0.81 after 3 hours and reached a peak of 1.21±0.76 after 1 day (P=0.03 and P=0.03, respectively) and then gradually decreased to 0.83±0.52 after 7 days, 0.78±0.42 after 14 days, and 0.72±0.30 after 6 months (P=0.22, P=0.29, and P=0.12, respectively). During a median follow-up period of 50.8 months, 31 first major cardiovascular events (death from cardiovascular causes, myocardial infarction, ischemic stroke, and coronary revascularization) occurred. After adjustment for age, sex, cardiovascular risk factors, and concomitant treatment with statins, increased Rho-associated kinase activity was associated with increasing risk of first major cardiovascular events (hazard ratio, 4.56; 95% confidence interval, 1.98–11.34; P<0.001). These findings suggest that Rho-associated kinase activity is dramatically changed after acute coronary syndrome and that Rho-associated kinase activity could be a useful biomarker to predict cardiovascular events in Japanese patients with acute coronary syndrome.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Japanese Patients 60 Years of Older With Atherosclerotic Risk-Factors: A Randomized Clinical Trial

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Japanese Patients 60 Years of Older With Atherosclerotic Risk-Factors: A Randomized Clinical Trial

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Japanese Patients 60 Years or Older With Atherosclerotic Risk Factors

Prevention of atherosclerotic cardiovascular diseases is an important public health priority in Japan due to an aging population. To determine whether daily, low-dose aspirin reduces the incidence of cardiovascular events in older Japanese patients with multiple atherosclerotic risk factors. The Japanese Primary Prevention Project (JPPP) was a multicenter, open-label, randomized, parallel-group trial. Patients (N = 14,464) were aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus recruited by primary care physicians at 1007 clinics in Japan between March 2005 and June 2007, and were followed up for up to 6.5 years, with last follow-up in May 2012. A multidisciplinary expert panel (blinded to treatment assignments) adjudicated study outcomes. Patients were randomized 1:1 to enteric-coated aspirin 100 mg/d or no aspirin in addition to ongoing medications. Composite primary outcome was death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal myocardial infarction. Secondary outcomes included individual end points. The study was terminated early by the data monitoring committee after a median follow-up of 5.02 years (interquartile range, 4.55-5.33) based on likely futility. In both the aspirin and no aspirin groups, 56 fatal events occurred. Patients with an occurrence of nonfatal stroke totaled 114 in the aspirin group and 108 in the no aspirin group; of nonfatal myocardial infarction, 20 in the aspirin group and 38 in the no aspirin group; of undefined cerebrovascular events, 3 in the aspirin group and 5 in the no aspirin group. The 5-year cumulative primary outcome event rate was not significantly different between the groups (2.77% [95% CI, 2.40%-3.20%] for aspirin vs 2.96% [95% CI, 2.58%-3.40%] for no aspirin; hazard ratio [HR], 0.94 [95% CI, 0.77-1.15]; P = .54). Aspirin significantly reduced incidence of nonfatal myocardial infarction (0.30 [95% CI, 0.19-0.47] for aspirin vs 0.58 [95% CI, 0.42-0.81] for no aspirin; HR, 0.53 [95% CI, 0.31-0.91]; P = .02) and transient ischemic attack (0.26 [95% CI, 0.16-0.42] for aspirin vs 0.49 [95% CI, 0.35-0.69] for no aspirin; HR, 0.57 [95% CI, 0.32-0.99]; P = .04), and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization (0.86 [95% CI, 0.67-1.11] for aspirin vs 0.51 [95% CI, 0.37-0.72] for no aspirin; HR, 1.85 [95% CI, 1.22-2.81]; P = .004). Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors. clinicaltrials.gov Identifier: NCT00225849.

Neutrophil/lymphocyte ratio as a predictor of cardiovascular events in incident dialysis patients: a Japanese prospective cohort study.

Previous studies have suggested that high neutrophil/lymphocyte ratios are related to worse outcome in patients with cardiovascular diseases. Patients with end-stage renal disease, especially those with inflammation, are at an increased risk of premature mortality, primarily because of cardiovascular disease. We aimed to clarify if high neutrophil/lymphocyte ratio is associated with increasing cardiovascular events in Japanese patients with end-stage renal disease. We enrolled 86 incident Japanese dialysis patients (58 men, age 58 ± 11 years) in a prospective cohort study. The median follow-up was for 38.7 months. The association between neutrophil/lymphocyte ratio at the start of dialysis therapy and clinical biomarkers was investigated. Relative risks and cumulative cardiovascular disease events were calculated. The median neutrophil/lymphocyte ratio reported was 3.72. The duration from the start of the dialysis therapy to the first cardiovascular disease event was significantly shorter as a neutrophil/lymphocyte ratio increased (log-rank test, P = 0.003). The relative risk of cardiovascular disease events in patients with neutrophil/lymphocyte ratio > median to cardiovascular events in patients with the ratio < median as a reference was 3.02 (95 % CI 1.32-8.00) in a Cox proportional hazard model. The cumulative cardiovascular disease events during the observational period was higher in patients with neutrophil/lymphocyte ratio > median (23.0 events 100 person-years) than in patients with the ratio < median (6.8 events 100 person-years). A higher neutrophil/lymphocyte ratio is associated with increased risk of cardiovascular disease events and is a stronger predictor of future events.

Disease duration and severity impacts on long-term cardiovascular events in Japanese patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) increases the mortality and morbidity of cardiovascular disease (CVD). However, the relationship between RA and the risk of CVD in the Japanese population remains unclear. Methods and resultsThis study comprised 571 RA patients who were admitted to Juntendo University Hospital from January 1990 to December 2000. Cardiovascular events (CVEs) were defined as cardiac death, acute coronary syndrome (ACS), symptomatic stroke, and congestive heart failure. During follow-up (mean 11.7±5.8 years), 7.5% of the patients died from all causes and 11.0% experienced CVEs. The morbidity of stroke and ACS was 3.6 and 2.5 per 1000 person-years, respectively. The mean RA disease duration at enrolment was significantly longer in patients who experienced CVEs than in those who did not experience CVEs (15.0±12.7 years vs. 10.8±9.7 years; p=0.01). Physical disabilities due to RA were more severe in patients who experienced CVEs than in those who did not experience CVEs. Patients with a long RA disease duration showed significantly higher event rates (p=0.033). Cox proportional hazards analysis identified a longer RA duration as an independent risk factor for CVD (hazard ratio 1.57, 95% CI 1.09–2.30, p=0.02). ConclusionJapanese RA patients showed a relatively high incidence of CVD, despite the fact that they had few coronary risk factors. The RA disease duration was an independent risk factor for CVEs.

Carotid intima-media thickness progression predicts cardiovascular events in Japanese patients with type 2 diabetes

AimsThe aim of this retrospective study was to investigate the relationship between progression of carotid intima-media thickness (cIMT) and cardiovascular events in Japanese patients with type 2 diabetes mellitus (T2DM) and free of history of cardiovascular events. MethodsPatients with T2DM (n=342) without history of cardiovascular events whose cIMT was assessed more than twice by ultrasonography were recruited and followed up for cardiovascular events. ResultsDuring a mean follow-up of 7.6 years, 56 (16.4%) cardiovascular events (27 coronary events and 29 cerebrovascular events) were recorded. Multivariate analysis with the Cox proportional hazard model identified cIMT progression as a significant determinant of cardiovascular events, with a hazard ratio (HR) of 2.24 (95% confidence interval; CI, 1.25–4.03, P<0.01), in addition to baseline cIMT. The Kaplan–Meier curves also showed significantly higher event rate in patients with high cIMT progression compared with those with low cIMT progression (log-rank χ2=6.65; P<0.01). Furthermore, the combination of high baseline cIMT and high cIMT progression was a significant predictor of cardiovascular events. ConclusionOur findings suggest that cIMT progression, in addition to baseline cIMT, is a predictor of cardiovascular events in patients with T2DM without history of cardiovascular events, and that the combination of cIMT progression and baseline cIMT has a strong predictive power for such events.

Improved prediction of cardiovascular events in diabetic patients: Role of quantitative ultrasonic tissue characterization.

The early prediction of cardiovascular disease in patients with type 2 diabetes has been a subject of great interest for decades. This issue has become critical, as the number of individuals with diabetes is soaring, many of them remain under suboptimal control1, and the burden of cardiovascular complications of diabetes is overwhelming in both developed and developing countries. In addition to well‐known demographic and metabolic characteristics, both genetic and non‐genetic risk factors have been shown to have a certain value in predicting cardiovascular events2. However, current cardiovascular risk assessment does not fully take into account the subsequent events, partly because these risk factors do not directly reflect functional and structural changes in vascular lesions. Thus, recent studies using non‐invasive image techniques targeting vascular structure might provide additional information in predicting clinical cardiovascular disease (Figure 1). In this regard, Katakami et al.4 reported that the application of ultrasonic tissue characterization of carotid plaque could improve the prediction of cardiovascular events in Japanese patients with type 2 diabetes.

Metabolic syndrome is not a predictor for cardiovascular events in Japanese patients with diabetes mellitus asymptomatic for coronary artery disease: A retrospective analysis of the J-ACCESS-2 study

PurposePatients with metabolic syndrome (MetS) have potentially higher risk for cardiovascular events. The aim of this study was to evaluate the effect of MetS on cardiac events in type-2 diabetic patients asymptomatic for coronary artery disease (CAD) in a Japanese population. MethodsA total of 485 patients from a J-ACCESS-2 investigation with stress-gated myocardial perfusion imaging (MPI) and quantitative-gated MPI analysis were examined. Cardiovascular hard events (cardiac death and acute coronary syndrome) and total events during a 3-year follow-up were analyzed. ResultsThe MetS group (n = 229) had higher incidence of hypertension, dyslipidemia, and ventricular dilatation than the non-MetS group (n = 256). The hard events were 8 and 12 for the MetS and non-MetS groups (P = n.s.), and total events were 31 and 31 for each of these groups, respectively (P = n.s.). Significant variables related to total cardiovascular events included age, current smoking, insulin use, total cholesterol, ejection fraction, summed stress score ≥ 9, and summed difference score ≥ 2. Cox proportional hazard analysis and Kaplan-Meier survival analysis showed that only the summed stress score was related to total events (P = .01), and the presence and the number of items for MetS criteria were not. ConclusionIn patients with type 2 diabetes asymptomatic for CAD, cardiovascular events and ischemia are as common in diabetic patients without MetS as in those with MetS. A high MPI defect score is related to total events including cardiac and cerebrovascular events.