Intima-Media Thickness in the Carotid Bifurcation is Related to Silent Brain Infarction: A Cross-Sectional Study.

AIMS: Carotid intima-media thickness (IMT) measurement is used to assess subclinical atherosclerosis. We aimed to examine the association between the maximum IMT by location and the occurrence of silent brain infarction (SBI). METHODS: Overall, 280 Japanese individuals (92 females, 52.6±5 years old) underwent a medical check-up at our hospital in Tokyo in 2015. Carotid IMT was measured at each site on ultrasound images (common carotid artery [CCA], internal carotid artery, or bifurcation). The risk factors for arterial dysfunction were evaluated. SBI was assessed using magnetic resonance imaging (MRI). The cross-sectional relationship between carotid maximum IMT and SBI was evaluated. RESULTS: Of the 280 individuals, 18 (6.4%) were diagnosed with SBI on MRI. The mean age of the SBI(-) and SBI(+) groups was 51.9±10.6 and 63.6±18.6 years, respectively. The correlation coefficients between the carotid maximum IMT at each location were very weak (correlation coefficient range: 0.180-0.253). The percentage of participants with SBI increased significantly with increasing maximum CCA and bIMT values. After adjusting for confounders, SBI was found to be significantly associated with the maximum bIMT (per 0.1-mm increase) (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI]: 1.03-1.17). When bIMT was categorized according to three groups (＜1.0 mm, 1.0-＜2.0 mm, and ≥ 2.0 mm), a significant SBI risk was also observed with an increase by each category of bIMT (aOR: 3.96, 95% CI: 1.63-9.52, P=0.002). CONCLUSION: The maximum bIMT was found to be the main determinant of SBI. A significant SBI risk was associated with an increase in each category of the maximum bIMT. Therefore, the maximum bIMT might be a useful predictor of future stroke in Japanese stroke-free medical check-up participants.

Adjunctive Catheter-Directed Thrombolysis during Primary PCI for ST-Segment Elevation Myocardial Infarction with High Thrombus Burden.

BACKGROUND: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet been established. METHODS: We assessed the adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. CDT was defined as intracoronary infusion of tissue plasminogen activator (t-PA; monteplase). RESULTS: Among the 1849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received t-PA (CDT group), whereas 222 did not receive it (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p = 0.53; 7.3% vs. 2.3%, p = 0.11; and 12.6% vs. 17.5%, p = 0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6% CDT group and 87.4% non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p < 0.01). However, the final rates improved without significant difference (90.3% vs. 97.4%, p = 0.14). CONCLUSIONS: Adjunctive CDT appears to be tolerated and feasible for high thrombus burden. Particularly, it may be an option in cases with failed aspiration thrombectomy.

Clinical Characteristics, Achievement of Secondary Prevention Goals, and Outcomes of Patients with Recurrent Acute Coronary Syndrome.

BACKGROUND: Because development of acute coronary syndrome (ACS) worsens the prognosis of patients with coronary artery disease, preventing recurrent ACS is crucial. However, the degree to which secondary prevention treatment goals are achieved in patients with recurrent ACS is unknown. METHODS: 214 consecutive ACS patients were classified as having First ACS (n=182) or Recurrent ACS (n=32), and the clinical characteristics of these groups were compared. Fifteen patients died or developed cardiovascular (CV) events during hospitalization, and the remaining 199 patients were followed from the date of hospital discharge to evaluate subsequent CV events. RESULTS: Patients in the Recurrent ACS group were older than those in the First ACS group (76.8±10.8 years vs 68.8±13.4 years, p=0.002) and had a higher rate of diabetes mellitus (DM) (65.6% vs 36.8%, p=0.003). The rate of achieving a low-density lipoprotein cholesterol (LDL-C) level of <70 mg/dL in the Recurrent ACS group was only 28.1%, even though 68.8% of these patients were taking statins. An HbA1c level of <7.0% was achieved in 66.7% of patients with recurrent ACS who had been diagnosed with DM. Overall, 12.5% of patients with recurrent ACS had received optimal treatment for secondary prevention. CV events after hospital discharge were noted in 37.9% of the Recurrent ACS group and 21.2% of the First ACS group (log-rank test: p=0.004). However, recurrent ACS was not an independent risk factor for CV events (adjusted hazard ratio: 2.09, 95% confidence interval: 0.95 to 4.63, p=0.068). CONCLUSION: Optimal treatment for secondary prevention was not achieved in some patients with recurrent ACS, and achievement of the guideline-recommended LDL-C goal for secondary prevention was especially low in this population.

Gastrointestinal bleeding increases the risk of subsequent cardiovascular events in patients with acute cardiovascular diseases requiring intensive care.

Gastrointestinal (GI) bleeding worsens the outcomes of critically ill patients in the intensive care unit (ICU). Owing to a lack of corresponding data, we aimed to investigate whether GI bleeding during cardiovascular-ICU (C-ICU) admission in acute cardiovascular (CV) disease patients is a risk factor for subsequent CV events. Totally, 492 consecutive C-ICU patients (40.9% acute coronary syndrome, 22.8% heart failure) were grouped into GI bleeding (n = 27; 12 upper GI and 15 lower GI) and non-GI bleeding (n = 465) groups. Thirty-nine patients died or developed CV events during hospitalization, and 453 were followed up from the date of C-ICU discharge to evaluate subsequent major adverse CV events. The GI bleeding group had a higher Acute Physiology and Chronic Health Evaluation II score (20.2 ± 8.2 vs. 15.1 ± 6.8, p < 0.001), higher frequency of mechanical ventilator use (29.6% vs. 13.1%, p = 0.039), and longer C-ICU admission duration (8 [5-16] days vs. 5 [3-8] days, p < 0.001) than the non-GI bleeding group. The in-hospital mortality rate did not differ between the groups. Of those who were followed-up, CV events after C-ICU discharge were identified in 34.6% and 14.3% of patients in the GI and non-GI bleeding groups, respectively, during a median follow-up period of 228 days (log rank, p < 0.001). GI bleeding was an independent risk factor for subsequent CV events (adjusted hazard ratio: 2.23, 95% confidence interval: 1.06-4.71; p = 0.035). GI bleeding during C-ICU admission was independently associated with subsequent CV events in such settings.

Elevated C-reactive Protein Levels Independently Predict the Development of Prediabetes Markers in Subjects with Normal Glucose Regulation.

AIMS: Prediabetes is a precursor of diabetes and increases the risk of cardiovascular disease. Individuals with prediabetes reportedly have higher C-reactive protein levels, which is a risk factor for diabetes, relative to individuals with normal glucose regulation. Inflammation may play a role in the very early-phase deterioration of glucose metabolism, although there is insufficient knowledge regarding this relationship. Thus, we examined the association between serum C-reactive protein level and the development of three prediabetes markers. METHODS: This study included 743 subjects with normal glucose regulation at baseline who completed oral glucose tolerance tests at baseline and after approximately 5 years. Subjects with a history of cardiovascular disease were excluded. RESULTS: During the 5-year follow-up, 55 subjects developed isolated impaired glucose tolerance (IGT; 2h-plasma glucose levels of 7.8-11.0 mmol/L), 24 subjects developed isolated impaired fasting glucose (IFG; fasting plasma glucose levels of 6.1-7.0 mmol/L), 3 subjects developed IFG plus IGT, and 53 subjects developed isolated elevated glycated hemoglobin levels (HbA1c; level of 41-47 mmol/mol). The multivariate analysis revealed that, relative to the lowest quartile, the highest serum C-reactive protein quartile was independently associated with an increased risk of developing isolated elevated HbA1c levels (odds ratio: 2.95, 95% confidence interval: 1.16-7.51, P=0.024) and marginally associated with an increased risk of developing impaired glucose tolerance plus diabetes. However, C-reactive protein levels were not associated with an increased risk of developing IFG. CONCLUSIONS: Elevated serum C-reactive protein levels independently predicted elevated HbA1c levels, but not IFG.

Elevated cardio-ankle vascular index may be related to future stroke risk in Japanese subjects.

BACKGROUND: The cardio-ankle vascular index (CAVI) has been proposed as a useful parameter for arteriosclerotic diseases. However, whether it is associated with stroke risk in Japanese subjects remains unclear. METHODS: In total, 280 Japanese subjects (92 females, 52.6 ± 5 years old) underwent a medical check-up. CAVI value and risk factors for arterial dysfunction were evaluated; the predicted 10-year stroke risk was measured by the Japan Public Health Center study. RESULTS: Age, sex, body mass index, and systolic blood pressure were significant independent predictors of CAVI. CAVI values were significantly elevated in the high, compared with the medium-low and low predicted risk groups. A significant odds ratio (OR) for the high-risk group was noted in the highest quartile of CAVI values (OR, 14.67; 95% confidence interval [CI], 3.17-68.0), compared with the lowest quartile, after adjusting for potential confounders. A significant OR for very high predicted stroke risk was also found for each quartile increase (OR, 3.04; 95% CI, 1.87-4.94) and 1-standard deviation increase (OR, 2.24; 95% CI, 1.52-3.30) in CAVI value. CONCLUSION: Elevated CAVI values were related to an elevated predicted stroke risk, suggesting that CAVI could be a suitable surrogate marker for finding subjects at an increased risk of first-ever stroke.

Association Between Elevated C-Reactive Protein Levels and Prediabetes in Adults, Particularly Impaired Glucose Tolerance.

OBJECTIVES: Prediabetes is a precursor of diabetes and increases the risk for cardiovascular disease. A high C-reactive protein (CRP) level is a risk factor for diabetes, and individuals with prediabetes have higher CRP levels than those with normal glucose tolerance. In addition, systemic inflammation may play a role in the early-phase deterioration of glucose metabolism. We examined the association between serum CRP levels and prediabetes. METHODS: Overall, 4,101 subjects without diabetes underwent oral glucose tolerance tests. Levels of serum CRP were divided into quartiles; the lowest quartile was used as the reference when calculating odds ratios (ORs) and confidence intervals. Isolated fasting glucose, isolated glucose tolerance and elevated glycated hemoglobin levels (i.e. between 42 and 47 mmol/mol [6.0% to 6.4%]) were indicative of prediabetes. RESULTS: In the multiple logistic regression analysis, the ORs (95% confidence intervals) for impaired glucose tolerance, impaired fasting glucose and elevated glycated hemoglobin levels corresponding to the highest quartile of CRP levels were 1.67 (1.31 to 2.14); 1.62 (1.15 to 2.28); and 1.47 (1.14 to 1.90), respectively. In the stratified analysis, the ORs for impaired glucose tolerance were consistently higher in the uppermost quartile than in the reference quartile in both the presence and absence of hypertension or dyslipidemia. In contrast, the ORs for impaired fasting glucose in the uppermost quartile were higher only in the presence of hypertension and dyslipidemia, and the OR for elevated glycated hemoglobin levels in the uppermost quartile was higher only in the presence of hypertension. CONCLUSIONS: Elevated serum CRP levels are associated with prediabetes, particularly impaired glucose tolerance.

Dyslipidemia and the Risk of Developing Hypertension in a Working-Age Male Population.

BACKGROUND: Hypertension is one of the main comorbidities associated with dyslipidemia. This study aimed to examine the extent to which dyslipidemia increases the risk of developing hypertension in a Japanese working-age male population. METHODS AND RESULTS: We analyzed data from 14 215 nonhypertensive male workers (age 38±9 years) who underwent annual medical checkups. Subjects were followed up for a median of 4 years to determine new-onset hypertension, defined as blood pressure (BP) ≥140/90 mm Hg or use of antihypertensive medication. The associations between serum lipid levels and development of hypertension were examined. During the follow-up period, 1483 subjects developed hypertension. After adjusting for age, body mass index, impaired fasting glucose/diabetes, baseline BP category, alcohol intake, smoking, exercise, and parental history of hypertension, subjects with a total cholesterol (TC) level ≥222 mg/dL were at a significantly increased risk of developing hypertension (hazard ratio: 1.28; 95% CI: 1.06-1.56) compared to subjects with a TC level ≤167 mg/dL. Similar results were observed for subjects with high low-density lipoprotein cholesterol (LDLC) and non-high-density lipoprotein cholesterol (HDLC) levels. A U-shaped relationship was found between HDLC level and risk of hypertension; compared to the third quintile, the multiadjusted hazard ratio was 1.22 (95% CI: 1.03-1.43) in the lowest quintile and 1.34 (95% CI: 1.12-1.60) in the highest quintile. CONCLUSIONS: Elevated serum levels of TC, LDLC, and non-HDLC were associated with an increased risk of hypertension in working-age Japanese men. For HDLC, risk of hypertension was increased at both low and high levels.

A Proposal for the Optimal Management Target for Serum Non-High-Density Lipoprotein Cholesterol Level in Low-Risk Japanese Workers.

AIM: The Japan Atherosclerosis Society Guidelines for the Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012) indicate that the management target for serum non-high-density lipoprotein cholesterol (non-HDLC) level is 30 mg/dL higher than that for low-density lipoprotein cholesterol (LDLC) level. However, it remains unclear whether this value is applicable to subjects at a low risk of cardiovascular disease. This study aimed to propose the optimal management target for serum non-HDLC level in low-risk Japanese subjects. METHODS: Among 20,909 subjects who underwent annual medical checkup at a Japanese company in 2008, we analyzed the data of 17,023 subjects (14,352 men, mean age 37.8±8.6 years) in risk category I according to the JAS Guidelines 2012. The correlation between LDLC and non-HDLC levels was examined. RESULTS: A strong correlation was found between LDLC and non-HDLC levels (r=0.95, p<0.001). The following regression equation for calculation of non-HDLC was obtained from linear regression analysis: non-HDLC (mg/dL)=1.09×LDLC (mg/dL)＋7.79. According to this equation, the optimal management target for non-HDLC level corresponding to that for LDLC level (160 mg/dL) was 180 mg/dL. A multiple logistic regression analysis revealed that age, obesity, habitual alcohol intake, and current smoking were significantly associated with non-HDLC ≥180 mg/dL. CONCLUSIONS: The management target for non-HDLC level is recommended to be set at 20 mg/dL higher than that for the LDLC level (i.e., 180 mg/dL) in low-risk Japanese subjects.

Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure patients with dyslipidemia.

AIMS: The effects of eicosapentaenoic acid (EPA) on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure (CHF) patients with dyslipidemia remain unclear. METHODS: A total of 139 CHF patients with a mean left ventricular ejection fraction (LVEF) of 37.6± 8.0% were divided into two groups based on whether EPA was included in their treatment regimen: the EPA group (n=71) and the no EPA group (n=68). Only patients with dyslipidemia at baseline (entry) were treated with EPA. The monocyte chemoattractant protein (MCP)-1 and asymmetric dimethylarginine (ADMA) levels were measured at baseline and after 12 months of treatment. RESULTS: At 12 months, in the EPA group, the LVEF had improved and the MCP-1 and ADMA levels had decreased (respectively, p＜0.001); however, in the no EPA group, the LVEF had worsened, while the MCP-1 and ADMA levels had increased (respectively, p＜0.001). Fifty-five patients experienced cardiac events, including 15 cardiac deaths and 40 readmissions for worsening of CHF during a median follow-up period of 28.0 months. The percent change in LVEF from baseline was found to be significantly associated with the percent change in ADMA (r=-0.462, p＜0.001). A multivariate Cox hazard analysis showed EPA treatment (hazard ratio: 0.21, 95% confidence interval: 0.05-0.93, p=0.031) to be an independent predictor of cardiac events. CONCLUSIONS: These data indicate that EPA treatment may improve the cardiac function and long-term prognosis of CHF patients with dyslipidemia, at least in part, due to reductions in inflammation and improvements in the endothelial function.

Effect of insulin resistance associated with compensatory hyperinsulinemia on the long-term prognosis in patients with vasospastic angina.

BACKGROUND: Insulin resistance associated with compensatory hyperinsulinemia plays a significant role in the pathogenesis of cardiovascular diseases, including vasospastic angina (VSA). However, the effects of insulin resistance associated with hyperinsulinemia on the long-term prognosis in patients with VSA remain unclear. METHODS: A total of 265 selected patients with VSA and 56 control subjects with atypical chest pain were enrolled in the present study. Patients with VSA had a positive acetylcholine (ACh) provocation test with normal coronary angiograms, and control subjects had a negative ACh test and normal coronary angiograms. A 75-g oral glucose tolerance test was performed, and the plasma glucose and immunoreactive insulin (IRI) levels were measured before, and 30 min and 120 min (IRI 120) after the 75-g glucose load. RESULTS: During the median follow-up period of 90.0 months, thirty-one patients developed cardiac events, including 6 sudden cardiac deaths and 25 readmissions for acute coronary syndrome. Cardiac events occurred in 38.9% of the patients with an IRI 120 ≥ 80 µU/ml and only 1.6% of the patients with an IRI 120<80 µU/ml (log rank 77.220, p<0.001). A multivariate analysis showed that an IRI 120 ≥ 80 µU/ml (hazard ratio 27.49, 95% confidence interval: 4.66-162.10, p<0.001) was an independent predictor of cardiac events. CONCLUSIONS: These data indicate that insulin resistance associated with compensatory hyperinsulinemia increases the risk of cardiac events in VSA patients.