Akihisa Nishino

Increased circulating plasma lysophosphatidic acid in patients with acute coronary syndrome.

BACKGROUND The platelet activator lysophosphatidic acid (LPA) has recently been identified as an ingredient in oxidized LDL and it has been isolated from atherosclerotic plaques. The lysophospholipase D activity of autotaxin produces LPA extracellularly from lysophosphatidylcholine (LPC). The present study determines whether circulating LPA is associated with acute coronary syndrome (ACS). METHODS We enrolled 141 consecutive patients (age, 62.6±3.8 y; male, 69.2%) with ACS (n=38), stable angina pectoris (SAP; n=72) or angiographically normal coronary arteries (NCA; n=31). The relationships between LPA and other established biomarkers were examined. Concentrations of plasma LPA were determined using an enzymatic assay. RESULTS Concentrations of LPA significantly correlated with LPC (r=0.549), autotaxin (r=0.370) and LDL-C (r=0.307) (all p<0.01). Lysophosphatidic acid concentrations were significantly higher in patients with ACS than with SAP and NCA (p<0.01), but did not significantly differ between patients with SAP and NCA. Multivariate logistic regression analyses revealed that the highest LPA tertile was independently associated with ACS (odds ratio 1.99, 95% CI: 1.18-3.39, p=0.02). CONCLUSIONS The present study demonstrated that increased circulating plasma LPA concentrations are significantly associated with ACS.

Increased lysophosphatidic acid levels in culprit coronary arteries of patients with acute coronary syndrome

BACKGROUND Lysophosphatidic acid (LPA) is a platelet activator and highly thrombogenic lipid constituent of atherosclerotic plaque. However, whether or not LPA locally released from culprit lesions is associated with acute coronary syndrome (ACS) remains unclear. METHODS We studied 52 patients with ACS who were treated by emergency percutaneous coronary intervention and thrombectomy. Levels of LPA and other established biomarkers were enzymatically assayed in samples of culprit coronary arterial and systemic peripheral arterial blood. Levels of LPA and lysophosphatidylcholine (LPC) were measured in plasma, and those of autotaxin, soluble CD40 ligand (sCD40L), hs-CRP and Lp-PLA2 were measured in serum. RESULTS Median LPA levels were significantly higher in coronary (CB) than in peripheral (PB) arterial blood (p = 0.009). Levels of sCD40L were higher in CB than in PB, but the difference did not reach statistical significance (p = 0.177). In contrast, autotaxin and Lp-PLA2 levels were significantly higher in PB than in CB (p = 0.005 and p = 0.038, respectively). Levels of LPC and hs-CRP were also higher in PB than in CB (p = 0.129 and p = 0.121, respectively). Levels of LPA in both CB and PB were positively and significantly associated with those of LPC (r = 0.632, p < 0.01 and r = 0.465, p < 0.001). CONCLUSIONS Culprit coronary arteries of ACS contained significantly more LPA than the systemic arterial circulation. Higher LPA concentrations might be associated with the pathophysiology of ACS.

Long-term outcomes of women with coronary artery disease following complete coronary revascularization

BACKGROUND Although coronary artery disease (CAD) is less prevalent in women than in men, early mortality rate is higher in women with CAD than in men with CAD following coronary revascularization. In terms of the long-term outcomes after coronary revascularization, limited data are available. Especially, in the Japanese CAD population, no data about sex-related differences in long-term outcomes after coronary revascularization exist. The aim of this study was to compare long-term outcomes between men and women following complete revascularization in Japanese patients with CAD. METHODS We collected data from 1836 consecutive patients who underwent complete revascularization by percutaneous coronary interventions and/or bypass surgeries. All-cause and cardiac mortality and the incidence of stroke were compared between men and women. In addition to the univariate analysis, a multivariate Cox regression was carried out in order to adjust for differences in baseline characteristics. RESULTS There were 274 female patients (14.9%). They were older, had greater total cholesterol levels, and were more likely to have multivessel disease than men. During follow-up [mean (SD), 11.4 (2.9) years], 412 patients died (including 131 patients who died of cardiac causes), and 130 had a stroke. In the multivariate analysis, female patients did not have a significant risk for all-cause mortality (hazard ratio [HR], 1.01; p=0.993), cardiac mortality (HR, 1.41; p=0.256), or stroke (HR, 0.71; p=0.309). CONCLUSIONS In the present study involving CAD patients who underwent complete revascularization, we showed that, although women were older and had more unfavorable risk profiles, they did not have a greater risk of long-term all-cause mortality, cardiac mortality, or stroke incidence, compared to men.

Higher lipoprotein-associated phospholipase A2 levels are associated with coronary atherosclerosis documented by coronary angiography.

Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory marker of cardiovascular disease. The present study investigates associations between Lp-PLA2 and other important biomarkers in Japanese patients with coronary artery disease. Methods We measured Lp-PLA2 levels in 141 consecutive patients (age 62.6 ± 3.8 years; men 69.2%) with angiographic evidence of coronary artery disease (acute coronary syndrome [ACS]; n = 38), stable angina pectoris (SAP; n = 72) or with angiographically normal coronary arteries (NCA; n = 31). Results Levels of Lp-PLA2 significantly correlated with low-density lipoprotein-cholesterol (r = 0.302), homocysteine (r = 0.528) and paraoxonase (r = 0.401) in all patients (all P < 0.01). Levels of Lp-PLA2 were significantly higher in patients with coronary atherosclerosis (ACS and SAP) than with NCA (P < 0.05). Levels of highly sensitive C-reactive protein were significantly higher in patients with ACS than with SAP and NCA (both P < 0.05). Multivariate logistic regression analyses revealed that higher Lp-PLA2 levels were independently associated with coronary atherosclerosis (odds ratio: 1.058; 95% confidence interval: 1.012–1.121; P = 0.001). Conclusions Higher Lp-PLA2 levels are associated with coronary atherosclerosis independently of traditional coronary risk factors. Thus, Lp-PLA2 is a novel biomarker of coronary atherosclerosis in Japanese patients.

An adult case of polysplenia syndrome associated with sinus node dysfunction, dextrocardia, and systemic venous anomalies.

A 54-year-old woman was referred to our hospital for symptomatic sinus bradyarrhythmia with a sinus pause of 8 seconds. She was diagnosed with dextrocardia during childhood and discovered to have heterotaxy syndrome when she had an appendectomy during her teenager years. Chest and abdominal examinations by computed tomography showed multiple spleens located on the right side and abnormal drainages of the superior and inferior vena cava. Left isomerism was diagnosed by bilaterally bilobed lungs. Because of a patent bilateral superior vena cava, pacemaker leads were implanted using the right cephalic vein approach. Her fainting symptoms disappeared after pacemaker implantation.

Long‐Term Effect of Metabolic Syndrome With and Without Diabetes Mellitus on Coronary Revascularization in Japanese Patients Undergoing Percutaneous Coronary Intervention

Metabolic syndrome (MS) plays a crucial role in the long‐term prognosis and primary or secondary prevention of coronary artery disease, regardless of the presence or absence of diabetes mellitus (DM). We previously reported that after percutaneous coronary intervention (PCI), patients with MS had worse long‐term outcome. However, there is no evidence indicating the importance of MS with and without DM on re‐revascularization procedures in Japanese patients undergoing PCI.

Aortic and mitral valvular calcification in patients undergoing hemodialysis for 10 years or more and their prognosis

Valvular disease in hemodialysis (HD) patients occurs at a younger age and progresses faster compared with valvular changes due to aging in the general population [1]. The following can be involved in the mechanism of valvular calcification: parathyroid abnormality, aging, long-term HD, and calcium deposits in valves due to calciumbased drug or phosphate binder [2]. Valvular calcification can develop due to hypertension, diabetes mellitus (DM), dyslipidemia, renal anemia, blood access, and infective endocarditis [3]. In this study, we examined aortic valvular calcification (AVC) and mitral valvular calcification (MVC) in patients undergoing HD for 10 years or more. Computed tomography (CT) and echocardiography were used to detect calcification. Comparison was made between valvular calcification and risk factors for arteriosclerosis. In addition, prognosis of valvular disease was examined. The subjectswere 41patients undergoingoutpatientHD for 10 years ormore. Theywere 29men and 12women (mean age: 60±8 years and meandurationofHD: 20±7 years). Theunderlyingdiseasewas chronic glomerulonephritis (CGN) in 28 patients (mean duration of hemodialysis: 23±7 years), DM in 10 patients (12±1 years), and polycystic kidney disease in 3 patients (22±1 years). Non-contrast enhanced cardiac CT was performed with a 0.5-second scan time and 1 cm scan width to examine the presence or absence of AVC and MVC. Visual assessmentwasperformed to evaluate the density of calcification. In the same period, the followingwasmeasured just before HD in the two-day break between HD sessions: total cholesterol, high density lipoprotein cholesterol (HDLC), triglyceride, postprandial glucose, hemoglobin A1c, calcium (Ca), phosphorus (P), Ca-P product, and parathyroid hormone. Echocardiography was also performed. All numerical data were expressed as means±standard deviation. Comparison of measurements between groups was performed using Students unpaired t test. A p-value of less than 0.05 was defined to be statistically significant. Table 1 shows patient characteristics by underlying disease. AVCwas difficult to differentiate from aortic calcification and MVC from left circumflex artery calcification. In both AVC and MVC, the motion of the heart caused plus and minus density artifacts. Thus, the apparent density of calcification differed from the actual density, and determination of severity of valvular calcificationwas difficult using CT. Therefore, accurate comparison could not be performed between the results of blood tests and the degree of calcification. CTexamination revealed AVC in 38 of 41 patients, andMVCwas seen in all patients.When the density was examined in each patient, the visually assessed density tended to International Journal of Cardiology 164 (2013) 123–128