Toshiki Kawamiya

Nutrition Status Predicts Severity of Vascular Calcification in Non-Dialyzed Chronic Kidney Disease

BACKGROUND Vascular calcification is a major complication in chronic kidney disease (CKD) that increases the risk of adverse clinical outcomes. Geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that predicts poor prognosis in elderly subjects. The purpose of the present study was to evaluate the correlation between GNRI and severity of vascular calcification in non-dialyzed CKD patients.Methods and Results:We enrolled 323 asymptomatic CKD patients. To evaluate abdominal aortic calcification (AAC), we used aortic calcification index (ACI) determined on non-contrast computed tomography. The patients were divided into three groups according to GNRI tertile. Median ACI significantly decreased with increasing GNRI tertile (15.5%, 13.6%, and 7.9%, respectively; P=0.001). On multivariate regression analysis GNRI was significantly correlated with ACI (β=-0.15, P=0.009). We also investigated the combination of GNRI and C-reactive-protein (CRP) for predicting the severity of AAC. Low GNRI and high CRP were significantly associated with severe AAC, compared with high GNRI and low CRP (OR, 4.07; P=0.004). CONCLUSIONS GNRI was significantly associated with AAC in non-dialyzed CKD patients.

Association of a Polymorphism of BTN2A1 With Hypertension in Japanese Individuals

BACKGROUND We previously showed that the C→T polymorphism (rs6929846) in butyrophilin, subfamily 2, member A1 gene (BTN2A1) was associated with myocardial infarction in Japanese individuals. Given that hypertension is a major risk factor for myocardial infarction, the association of rs6929846 of BTN2A1 with myocardial infarction might be attributable, at least in part, to its effect on susceptibility to hypertension. We have thus examined the relation of rs6929846 of BTN2A1 to hypertension in Japanese individuals. METHODS A total of 8,567 Japanese individuals from two independent subject panels were examined: Subject panels A and B comprised 2,317 hypertensive individuals and 1,933 controls, and 2,911 hypertensive individuals and 1,406 controls, respectively. The genotype of rs6929846 was determined by a method that combines the PCR and sequence-specific oligonucleotide probes with suspension array technology. RESULTS Multivariable logistic regression analysis with adjustment for covariates revealed that rs6929846 of BTN2A1 was significantly associated with hypertension in subject panel A (P = 2.6 × 10(-6); odds ratio, 1.69) and in subject panel B (P = 0.0284; odds ratio, 1.24), with the T allele representing a risk factor for hypertension. The rs6929846 was associated with systolic blood pressure (BP) in subject panels A (P = 0.0063) and B (P = 0.0115) and with diastolic BP in subject panel B (P = 0.0323), with the T allele being related to high BP. CONCLUSIONS BTN2A1 may be a susceptibility gene for hypertension in Japanese individuals. Determination of genotype for this polymorphism may prove informative for assessment of the genetic risk for hypertension.

Impact of Geriatric Nutritional Risk Index on cardiovascular outcomes in patients with stable coronary artery disease

BACKGROUND The association between malnutrition and cardiovascular prognosis in patients with stable coronary artery disease remains unclear. The aim of this study was to evaluate the association between Geriatric Nutritional Risk Index (GNRI), a simple tool to assess nutritional risk, and long-term outcomes after elective percutaneous coronary intervention (PCI). METHODS This study consisted of 802 patients (age, 70±10 years, male, 69%) who underwent elective PCI. GNRI was calculated at baseline as follows: GNRI=[14.89×serum albumin (g/dl)+[41.7×(body weight/body weight at body mass index of 22)]]. Patients were then divided into three groups as previously reported: GNRI <92, 92 to ≤98, and >98. The endpoint of this study was the composite of cardiac death or non-fatal myocardial infarction. RESULTS During a median follow-up period of 1568 days, 56 cardiac events occurred. Using Kaplan-Meier analysis, the 4-year event-free rates were found to be 79% for GNRI <92, 90% for GNRI 92 to ≤98, and 97% for GNRI >98 (log-rank test p<0.001). GNRI <92 and GNRI 92 to ≤98 showed 6.76-fold [95% confidence interval (CI) 3.13-14.56, p<0.001] and 3.03-fold (HR 3.03, 95%CI 1.36-6.78, p=0.007) increase in the incidences of cardiac death or non-fatal myocardial infarction compared with GNRI >98 after adjusting for confounding factors. CONCLUSION GNRI significantly associated with cardiac events after elective PCI. Further studies should be performed to establish appropriate therapeutic strategies for this vulnerable patient group.

Association of polymorphisms of BTN2A1 and ILF3 with myocardial infarction in Japanese individuals with or without hypertension, diabetes mellitus or chronic kidney disease

Recent evidence suggests that genetic variants that confer susceptibility to myocardial infarction (MI) may differ between men and women or between individuals with or without conventional risk factors for MI. We previously showed that rs6929846 of BTN2A1 and rs2569512 of ILF3 were significantly associated with MI in Japanese individuals. In the present study, we examined the associations of rs6929846 of BTN2A1 or rs2569512 of ILF3 to MI among individuals stratified by the absence or presence of hypertension, diabetes mellitus (DM) and chronic kidney disease (CKD). The study population was comprised of 5689 unrelated Japanese individuals, including 1626 subjects with MI and 4063 controls with or without hypertension, DM or CKD. Multivariable logistic regression analyses with adjustment for covariates revealed that rs6929846 of BTN2A1 was significantly associated with MI in individuals with (P=0.0001; odds ratio, 1.49) or without (P=1.6x10-7; odds ratio, 2.32) hypertension; in individuals with (P=0.0002; odds ratio, 1.65) or without (P=8.1x10-7; odds ratio, 1.76) DM; and in individuals without CKD (P=6.0x10-11; odds ratio, 2.03), but not in those with CKD. Similar analyses revealed that rs2569512 of ILF3 was significantly associated with MI in individuals with (P=0.0041; odds ratio, 1.26) or without (P=0.0051; odds ratio, 1.78) hypertension; in individuals with (P=0.0200; odds ratio, 1.46) or without (P=0.0174; odds ratio, 1.43) DM; and in individuals with (P=0.0011, odds ratio, 1.47) or without (P=0.0237; odds ratio, 1.34) CKD. Results suggested that the association of rs6929846 in BTN2A1 with MI was more apparent in low-risk individuals than in high-risk individuals, whereas the association of rs2569512 in ILF3 with MI was not influenced by the absence or presence of hypertension, DM or CKD. Stratification of subjects based on hypertension, DM or CKD may thus be informative in order to achieve personalized prevention of MI with the use of genetic information.

Association of polymorphisms of BTN2A1 and ILF3 with myocardial infarction in Japanese individuals with different lipid profiles

Dyslipidemia is an important risk factor for myocardial infarction (MI). We previously showed that gene polymorphisms associated with MI differed among individuals with different lipid profiles. We also showed that rs6929846 of BTN2A1 and rs2569512 of ILF3 were significantly associated with MI in Japanese individuals. In the present study, we examined the relationship between rs6929846 of BTN2A1 or rs2569512 of ILF3 and MI in individuals with low or high serum concentrations of triglycerides, high density lipoprotein (HDL) cholesterol, or low density lipoprotein (LDL) cholesterol, respectively. The study population comprised 5513 unrelated Japanese individuals, including 1537 subjects with MI and 3976 controls. Multivariable logistic regression analyses with adjustment for covariates revealed that rs6929846 of BTN2A1 was significantly associated with MI in individuals with low (P=3.1 x 10-5; odds ratio, OR=1.66) or high (P = 1.1 x 10⁻⁶; OR = 2.09) triglycerides; in individuals with low (P = 0.0082; OR = 1.75) or high (P = 2.0 x 10⁻⁹; OR = 1.85) HDL cholesterol; and in individuals with low (P = 3.2 x 10⁻⁷; OR = 1.75) or high (P = 2.8 x 10⁻⁵; OR =2.18) LDL cholesterol. Similar analyses revealed that rs2569512 of ILF3 was significantly associated with MI in individuals with low (P = 0.0066; OR = 1.47) or high (P = 0.0013; OR = 1.88) triglycerides; in individuals with low (P = 0.0059; OR = 1.96) or high (P = 0.0020; OR = 1.51) HDL cholesterol; and in individuals with low (P = 0.0004, OR = 1.62) LDL cholesterol, but not in those with high LDL cholesterol. The results suggest that the relationship between rs6929846 of BTN2A1 or rs2569512 of ILF3 and MI is influenced by the serum concentrations of HDL and LDL cholesterol, respectively. Stratification of subjects according to lipid profiles may thus be useful for the personalized prevention of MI based on genetic information.

Correlations between geriatric nutritional risk index and peripheral artery disease in elderly coronary artery disease patients.

Malnutrition is associated with the development of atherosclerosis and an increased risk of cardiovascular mortality in elderly patients. The present study aimed to investigate the association between the Geriatric Nutritional Risk Index (GNRI), a simple nutritional assessment tool, and the prevalence of peripheral artery disease (PAD) in elderly coronary artery disease patients.

Decreased Serum Albumin Predicts Bleeding Events in Patients on Antiplatelet Therapy After Percutaneous Coronary Intervention

BACKGROUND Antiplatelet therapy (APT) after percutaneous coronary intervention (PCI) prevents ischemic events with increased risk of bleeding. Little is known about the relationship between hypoalbuminemia and bleeding risk in patients receiving APT after PCI. This study investigated the association between serum albumin level and bleeding events in this population.Methods and Results:We enrolled 438 consecutive patients who were prescribed dual APT (DAPT; aspirin and thienopyridine) beyond 1 month after successful PCI without adverse events. The patients were divided into 3 groups according to serum albumin tertile: tertile 1, ≤3.7 g/dL; tertile 2, 3.8-4.1 g/dL; and tertile 3, ≥4.2 g/dL. Adverse bleeding events were defined as Bleeding Academic Research Consortium criteria types 2, 3, and 5. During the median follow-up of 29.5 months, a total of 30 adverse bleeding events were observed. Median duration of DAPT was 14 months. The tertile 1 group had the highest risk of adverse bleeding events (event-free rate, 83.1%, 94.3% and 95.8%, respectively; P<0.001). On Cox proportional hazards modeling, serum albumin independently predicted adverse bleeding events (HR, 0.10, 95% CI: 0.027-0.39, P=0.001, for tertile 3 vs. tertile 1). CONCLUSIONS Decreased serum albumin predicted bleeding events in patients with APT after PCI.

Impact of Paradoxical Decrease in High-density Lipoprotein Cholesterol Levels After Statin Therapy on Major Adverse Cardiovascular Events in Patients with Stable Angina Pectoris

PURPOSE Statin therapy usually increases HDL-C levels. However, a paradoxical decrease in HDL-C levels after statin therapy is often seen in clinical settings. The relationship between a paradoxical decrease in HDL-C levels after statin therapy and adverse cardiovascular events in patients with stable angina pectoris (SAP) is not well understood. The purpose of this study was to analyze the relationship between paradoxical HDL-C decreases after statin therapy and major adverse cardiovascular events (MACEs) in patients undergoing percutaneous coronary intervention (PCI) for SAP. METHODS Between January 2006 and March 2015, 867 patients underwent PCI for SAP. Of them, we enrolled 209 patients who were newly started on statin therapy before PCI. We excluded patients who had started statin therapy earlier than 6 months before PCI, patients who had not started statin therapy after PCI, and patients who were diagnosed with acute coronary syndrome. They were divided into 2 groups according to the change in their HDL-C levels between baseline and 6 to 9 months after the index PCI: decreased HDL group after statin treatment (80 patients) and increased HDL group (129 patients). The primary end points were MACEs defined as a composite of all-cause death, nonfatal acute myocardial infarction, and target vessel revascularization (TVR). FINDINGS Using Kaplan-Meier analysis, the 7-year event rate for composite MACEs in the decreased HDL group was found to be higher than that for the increased HDL group (38% versus 24%, log-rank P = 0.02). TVR occurred more frequently in the decreased HDL group than in the increased HDL group (32% versus 12%, log-rank P = 0.01). With the use of multivariate analysis, changes in HDL-C levels after statin therapy indicated a significant inverse association with the increased risk of MACEs, (hazard ratio [HR] = 0.94; 95% CI, 0.92-0.97; P < 0.01). The incidence of MACEs was more strongly associated with ΔHDL than with ΔLDL. Moreover, BMS usage also independently predicted MACEs (HR = 2.18; 95% CI, 1.14-4.17; P < 0.01). IMPLICATIONS A paradoxical decrease in HDL-C levels after statin therapy might be a risk factor for MACEs, especially TVR, in patients with SAP.

Impact of Coronary Stent Fracture on Restenotic Neointimal Tissue Characterization After Drug-Eluting Stent Implantation: An Integrated Backscatter Intravascular Ultrasound Study

Although drug-eluting stents (DESs) reduce the rates of in-stent restenosis (ISR) and subsequent target lesion revascularization, stent fracture (SF) after DES implantation has become an important concern because of its potential association with restenosis and stent thrombosis. We aimed to assess the pathogenic impact of SF on in-stent restenotic neointimal tissue components after DES implantation. We analyzed 43 consecutive patients (14 with SF and 29 without SF) with ISR requiring revascularization after DES implantation between January 2008 and March 2014. For evaluation of in-stent tissue components, integrated backscatter intravascular ultrasound (IB-IVUS) was performed. SF was defined as complete or partial separation of stent segments observed using plain fluoroscopy or intravascular ultrasound. On volumetric IB-IVUS analyses, patients with SF had a significantly higher percentage of lipid tissue volume within the neointima and a significantly lower percentage of fibrous tissue volume than those without (37.3 ± 18.9% versus 24.9 ± 12.4%, P = 0.02, and 61.2 ± 18.3 versus 72.6 ± 12.1%, P = 0.04, respectively). Moreover, SF was positively correlated with the percentage of lipid volume on multiple linear regression analysis after adjustment for confounding factors (β = 0.36, P = 0.03). The interval from stent implantation was similar in both groups (47.0 ± 28.7 versus 37.7 ± 33.3 months; P = 0.39). In conclusion, SF is associated with larger lipid tissue volume within the neointima after DES placement, suggesting a contribution to the development of neoatherosclerosis and vulnerable neointima. Thus SF might lead to future adverse coronary events.

Prognostic Value of Tissue Inhibitor of Metalloproteinase in Acute Aortic Dissection

Background: Increases in levels of matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) occur in acute aortic dissection (AAD); however, their association with prognosis in AAD remains largely unknown. We studied the use of MMP and TIMP in predicting long-term outcomes in medically controlled AAD patients. Methods: A total of 82 patients were enrolled (15 Stanford Type A and 67 type B, age 65.1±13.3). AAD was diagnosed by enhanced CT, with serial imaging studies during follow-up. Blood tests for MMP-2, MMP-9, TIMP-1, and TIMP-2 were performed within a week after symptom onset. Results: A poor outcome due to death or aortic surgical repair occurred in 17 patients, classified as an unfavorable group. The remaining 65 patients were classified into a favorable group. By multivariate analysis maximum dissection diameter (MDD), TIMP-1, and TIMP-2 were significantly associated with an unfavorable outcome (P 3.34) had significant predictive power (sensitivity 88.2%, specificity 80.0%). Patients with MDD � 46.8 mm and a TIMP-1/TIMP-2 ratio � 3.34 had a significantly poorer outcome (log rank P < 0.0001). Similarly, in Cox regression analysis AAD patients with MDD � 46.8 mm and a TIMP- 1/TIMP-2 ratio � 3.34 had the highest risk for an unfavorable outcome (P < 0.001, hazard ratio 45.6, 95% confidence interval 5.96 to 348.42). Conclusion: In AAD a higher TIMP-1/TIMP-2 ratio was significantly associated with an increased risk of death or surgical repair.