Pravastatin improves postprandial endothelial dysfunction and hemorheological deterioration in patients with effort angina pectoris.

Postprandial hypertriglyceridemia and hyperglycemia may promote endothelial and hemorheological dysfunction. The present study investigated the effects of pravastatin on endothelial function and hemorheology in patients with stable angina pectoris (AP) before and after eating a test meal. We recruited 26 patients with stable AP who had impaired glucose tolerance and mild dyslipidemia and six healthy men as controls to assess endothelial function and hemorheological behavior. In each group, we measured forearm blood flow (FBF) during post-ischemic reactive hyperemia and obtained blood samples before and 2 h after the test meal. Pravastatin 20 mg/day was then commenced in the 26 AP patients. The above tests were repeated after 2 days and 6 months. Maximum FBF during hyperemia in the baseline fasting phase was significantly lower in the AP patients than in the controls (p < 0.05). Fasting and postprandial FBF during reactive hyperemia time-dependently improved after pravastatin treatment (p < 0.05 vs. baseline data for each phase). Pravastatin treatment for 6 months, but not for 2 days, inhibited leukocyte activation and improved hemorheological parameters. In conclusion, pravastatin treatment for 6 months improved fasting and postprandial endothelial and hemorheological dysfunction in AP patients.

Effects of pitavastatin on walking capacity and CD34+/133+ cell number in patients with peripheral artery disease.

This multi-center prospective non-randomized comparative study investigated the effects of pitavastatin in patients with peripheral artery disease (PAD) in terms of exercise tolerance capacities and peripheral CD34+/133+ cell numbers. At baseline, a peripheral blood test was administered to 75 patients with PAD, along with a treadmill exercise test using the Skinner-Gardner protocol to measure asymptomatic walking distance (AWD) and maximum walking distance (MWD). Each patient was assigned to a 6-month pitavastatin treatment group (n = 53) or a control group (n = 22), according to the patient's preference. The tests were repeated in both groups at 3 and 6 months. Baseline AWD and MWD correlated positively with the ankle-brachial pressure index (r = 0.342, p = 0.0032 and r = 0.324, p = 0.0054, respectively). Both AWD and MWD values improved at 3 and 6 months compared with baseline, and the degrees of their improvement were higher in the pitavastatin treatment group. CD34+/133+ cell numbers did not change over time or between groups. Eighty-seven percent of patients in the treatment group attained low-density lipoprotein cholesterol levels below 100 mg/dL after 3 months. The study shows that pitavastatin may be effective in increasing exercise tolerance capacity in patients with PAD.

Lower 1,5-anhydroglucitol is associated with adverse clinical events after percutaneous coronary intervention.

Diabetes mellitus and impaired glucose tolerance are well-known risk factors for coronary artery disease (CAD) and adverse clinical events after percutaneous coronary intervention (PCI). Postprandial hyperglycemia is an important risk factor for CAD and serum 1,5-anhydroglucitol (1,5-AG) reflects postprandial hyperglycemia more robustly than hemoglobin (Hb)A1c. We aimed to clarify the relationship between serum 1,5-AG level and adverse clinical events after PCI. We enrolled 141 patients after PCI with follow-up coronary angiography. We evaluated associations between glycemic biomarkers including HbA1c and 1,5-AG and cardiovascular events during follow-up. Median serum 1,5-AG level was significantly lower in patients with any coronary revascularization and target lesion revascularization (TLR) [13.4 µg/ml (first quartile, third quartile 9.80, 18.3) vs. 18.7 (12.8, 24.2), p = 0.005; 13.4 µg/ml (10.2, 16.4) vs. 18.7 (12.9, 24.2), p = 0.001, respectively]. Multivariate logistic analysis showed lower 1,5-AG was independently associated with any coronary revascularization and TLR (odds ratio 0.93, 95 % confidence interval 0.86-0.99, p = 0.04; 0.90, 0.81-0.99, p = 0.044, respectively), whereas higher HbA1c was not. Postprandial hyperglycemia and lower 1,5-AG are important risk factors for adverse clinical events after PCI.

Implications of pentraxin 3 levels in patients with acute aortic dissection.

Acute aortic dissection (AAD) causes transient inflammation with occasional pleural fluid (PF) accumulation. Although pentraxin 3 (PTX3) is a vascular inflammation-related biomarker, little is known about PTX3 levels in patients with AAD. We explored the serial changes in plasma PTX3 levels and the association of peak levels with the amount of PF accumulation. Consecutive patients (n = 41) with Stanford type B AAD were enrolled, and blood samples for the measurements of serum albumin, plasma PTX3 and high-sensitivity C-reactive protein (CRP) were collected daily until 7 days after symptom onset. PF accumulation on computed tomography imaging on the third hospital day was divided into 3 grades (I: none or slight, II: mild in the uni- or bilateral pleural cavity, III: moderate or more). PTX3 and CRP levels were analyzed after logarithmic transformation because of their skewed distributions. Peak PTX3 and CRP levels were observed at 4.3 ± 2.1 and 4.7 ± 2.0 days after symptom onset, and their values were 12.2 [interquartile range (IQR), 8.2-20.9] ng/mL and 12.0 (IQR, 8.6-15.2) mg/dL, respectively. On univariate analysis, the peak level of PTX3 had a negative correlation with the minimum level of serum albumin, and a positive correlation with PF grade and duration of intensive care unit stay. On multivariate analysis, the peak level of PTX3 was correlated with PF grade (P = 0.037). In conclusion, the peak level of PTX3 in patients with AAD was associated with the amount of transient PF accumulation, which may be associated with inflammatory vascular permeability.

Dipeptidyl peptidase-4 inhibitors are associated with improved left ventricular diastolic function after acute myocardial infarction in diabetic patients.

Dipeptidyl peptidase-4 (DPP4) is an integral membrane glycoprotein that modulates the pathological state of diabetes mellitus (DM), and DPP4 inhibitors are a new class of anti-type-2 DM drugs. Recent preclinical studies have associated DPP4 inhibition with improved myocardial systolic and diastolic function. Based on preclinical findings, we investigated associations between the administration of DPP4 inhibitors and cardiac function after acute myocardial infarction (AMI) in a clinical setting. We enrolled 34 patients with diabetes who were treated for acute myocardial infarction at our hospital between January 2010 and December 2012. We retrospectively compared changes in cardiac parameters determined by trans-thoracic echocardiography between patients treated with (DPP4-I group; n = 13) or without (non-DPP4-I group; n = 21) a DPP4 inhibitor during follow-up. The values of E/e' and of e'/a' significantly decreased and increased, respectively, in the DPP4-I, compared with the non-DPP4-I group (-2.53 ± 5.53 vs. 2.58 ± 5.68, p = 0.038 and 0.08 ± 0.23 vs. -0.12 ± 0.21, p = 0.036, respectively). We concluded that DPP4 inhibitors could improve E/e' and e'/a' in patients with DM and AMI and thus might be effective for treating left ventricular diastolic failure.

Lower 1,5-anhydroglucitol is associated with denovo coronary artery disease in patients at high cardiovascular risk.

Postprandial hyperglycemia is a risk factor for cardiovascular disease and mortality. Serum 1,5-anhydroglucitol (1,5-AG) level is an useful clinical marker of glucose metabolism which reflects postprandial hyperglycemia more robustly compared to hemoglobin A1c (HbA1c). Relationship between serum 1,5-AG level and cardiovascular disease has been reported; however, comparison between HbA1c and 1,5-AG as markers of cardiovascular disease was not performed. We included 227 consecutive patients who underwent coronary angiography meeting the following inclusion criteria: (1) patients who had no history of coronary artery disease (CAD); (2) patients without acute coronary syndrome; (3) patients without poorly controlled diabetes mellitus; (4) patients without anemia, liver dysfunction, acute, and chronic renal failure and malnutrition; and (5) patients without adhibition of acarbose or Chinese herbal medicine. We measured HbA1c, glycoalbumin, and 1,5-AG. Serum 1,5-AG was significantly lower in patients with CAD (16.6 ± 8.50 vs. 21.1 ± 7.97 µg/ml, P < 0.001). Multivariable logistic regression analysis showed decrease in serum 1,5-AG was independently associated with the presence of denovo CAD (0.93, 95% CI 0.88-0.98, P = 0.006). Serum 1,5-AG was also independently associated with the presence of denovo CAD in patients without diabetes mellitus (0.94, 95% CI 0.88-0.99, P = 0.046). In conclusion, lower serum 1,5-AG was associated with the presence of denovo CAD. Serum 1,5-AG may identify high cardiovascular risk patients for denovo CAD in both diabetic and non-diabetic patients.

Transient retinopathy in acute aortic dissection.

PURPOSE: To explore the occurrence of transient retinopathy and its prognostic importance in patients with acute aortic dissection (AAD). DESIGN: Prospective, observational study. PARTICIPANTS: Sixty-four patients with Stanford type B AAD were treated with conservative medical therapy. METHODS: Retinopathy findings, such as cotton-wool spots and hemorrhage, were examined. Fundus photography was performed on hospital days 9 to 14 and after 2 or 3 months. The association between the appearance of retinopathy and the subsequent cardio-cerebrovascular events was investigated. MAIN OUTCOME MEASURES: The primary outcomes included the incidence of retinopathy and subsequent adverse cardio-cerebrovascular events. RESULTS: Retinopathy was detected in 55% (35 of 64) of patients (cotton-wool spots alone, n = 31; dot hemorrhage alone, n = 1; and both, n = 3). These findings disappeared in all 12 patients who underwent follow-up fundus examinations. In the multivariate analysis, a history of hypertension and higher peak C-reactive protein level were independently associated with retinopathy. At a median follow-up of 911 days, adverse cardio-cerebrovascular events were reported in 11 patients, of whom those with retinopathy experienced adverse events significantly more frequently than those without retinopathy (P = 0.045). CONCLUSIONS: Retinopathy occurred frequently in patients with AAD. This retinopathy was associated with a history of hypertension and higher peak C-reactive protein levels and was an important predictive factor for adverse cardio-cerebrovascular outcomes.

Transient no reflow following primary percutaneous coronary intervention.

No reflow following primary percutaneous coronary intervention (PCI) is a serious complication in the treatment of acute myocardial infarction. No reflow in some patients is reversible (transient no reflow), whereas no reflow in others persists until the end of the procedure (persistent no reflow). The aim of this study was to identify clinical features of transient no reflow following primary PCI. Consecutive patients with no reflow (n = 123) were enrolled following primary PCI. Among them, 59 patients were in the transient group and 64 in the persistent group. We compared clinical features and hospital outcomes between the two groups. Multivariate logistic regression analysis was performed to identify the determinants of transient no reflow. The transient group had a lower rate of in-hospital cardiac death than the persistent group (0 vs. 6.4 %, relatively, P = 0.018). There was a trend for a shorter length of hospital stay in the transient group. Multivariate logistic regression analysis identified initial thrombolysis in myocardial infarction (TIMI) flow grade 3 (OR 6.239, 95 % CI 1.727-22.541, P = 0.005) and a higher estimated glomerular filtration rate (OR 1.204, 95 % CI 1.006-1.440, P = 0.042) as independent predictors of transient no reflow. Transient no reflow tended to be associated with TIMI thrombus grade ≤3 (OR 2.879, 95 % CI 0.928-8.931, P = 0.067). In conclusion, initial TIMI flow grade 3 and preserved renal function were associated with recovery from no reflow. Initial angiographic finding such as TIMI flow or TIMI thrombus grade might be an important predictor of recovery from the no-reflow phenomenon.

Hyponatremia as a predictor for worsening heart failure in patients receiving cardiac resynchronization therapy.

BACKGROUND: Various factors associated with worsening heart failure (HF) events have been investigated in HF subjects. The purpose of this study was to identify the predictive factor(s) for worsening HF events after cardiac resynchronization therapy (CRT) among baseline parameters, as well as baseline factors associated with responsiveness or non-responsiveness to CRT. METHODS AND RESULTS: Seventy-seven HF patients with an indication for CRT were enrolled. Baseline parameters of blood chemistry, electrocardiogram, echocardiogram and cardiac catheterization before device implantation were measured, and subsequent clinical HF events after CRT were investigated. During the follow-up period (median 601 days), 22 of 77 (29%) recipients had HF events (unscheduled HF hospitalization: 16; use of left ventricular assist system: 1; heart transplantation: 1; cardiac death: 4). In the multivariate Cox proportional hazards model, low serum sodium concentration was associated with the occurrence of HF events after CRT (hazard ratio 0.82, 95% confidence interval 0.68-0.99, P=0.034). At baseline, serum sodium concentration negatively correlated with pulmonary capillary wedge pressure (r=-0.71, P<0.001) and with plasma arginine vasopressin level (r=-0.68, P=0.008). CONCLUSIONS: Hyponatremia is an independent predictor for worsening HF events after CRT implantation, which may be partly explained by elevated level of plasma arginine vasopressin.

Infective Arteritis Manifesting as an Acute Subdural Hematoma.

We encountered a 60-year-old man who had been diagnosed with heart failure of valvular disease and infective endocarditis; he was being treated with intravenous antibiotics and diuretics. On the 12th hospital day, he suddenly lost consciousness; computed tomography showed a right-sided huge subdural hematoma (SDH) with brain herniation. He died after invasive care was discontinued. A massive SDH was noted at autopsy, and microimaging demonstrated ruptured infective arteritis, without aneurysm, on the surface of the culprit lobe. Acute SDH usually occurs after head trauma, but an area of nonsaccular aneurysmal arteritis can also result in acute SDH.

A study of takotsubo syndrome over 9 years at the Tokyo Cardiovascular Care Unit Network Registry.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiovascular disease with clinical manifestations similar to those of acute myocardial infarction (AMI), and TTS sometimes occurs just after catastrophes. Large-scale studies of TTS in Japan are scarce, so we examined data over 9 years from Tokyo metropolitan acute cardiovascular care hospital network registry. METHODS: A total of 1626 patients were diagnosed with TTS between 2010 and 2018 at Tokyo Cardiovascular Care Unit Network facilities, and data from all these patients were analyzed. We investigated annual and monthly captured incidence of TTS, temporal trend of the captured incidence proportion of TTS versus AMI, the occurrence of TTS on the day of the great earthquake, and we elucidated the prognostic factors for in-hospital death. RESULTS: The annual incidence proportion of TTS versus AMI increased from 2.3 % to 4.5 % (p < 0.001) over 9 years. The mean TTS patient age was 74.4 years: the peak incidence of TTS was at 80 to 84 years of age for both male and female; females accounted for 78.5 % of patients. The monthly variation of the incidence of TTS was found (p = 0.009). In 2011, a total of 137 cases of TTS occurred, with as many as 6 occurring on March 11, the day of the Great East Japan Earthquake. There was a definable trigger for TTS in 64 % (physical: 36 %; emotional: 27 %; others: 2 %). All-cause in-hospital mortality was 5.3 % and was higher in males than in females (10.3 % vs 3.9 %; p < 0.001). Non-cardiac causes accounted for 62 % of in-hospital mortality. Factors at presentation that were associated with in-hospital all-cause mortality were male sex, low body mass index, and a high C-reactive protein level. CONCLUSIONS: This study elucidated the clinical features, in-hospital outcomes, and their attributed factors in patients with TTS in real-world clinical practice in Japan.

Impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome: A multicenter registry of the Tokyo Cardiovascular Care Unit Network.

BACKGROUND: Hypoalbuminemia is common in critically ill patients and is associated with poor outcomes. However, the relationship between serum albumin levels and clinical outcomes in patients with takotsubo syndrome remains unclear. We examined the impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome. METHODS: Using the multicenter registry of the Tokyo Cardiovascular Care Unit Network between January 2017 and December 2020, we identified 631 eligible patients with takotsubo syndrome (median age, 78 years; male proportion, 22 %) and documented serum albumin levels at admission, which were used to allocate patients to hypoalbuminemia (serum albumin <3.5 g/dL) or normal albumin (serum albumin ≥3.5 g/dL) groups. Patient characteristics and in-hospital mortality were compared between the groups. RESULTS: Hypoalbuminemia was detected in 200 (32 %) patients at admission. The hypoalbuminemia group was older and had a higher proportion of men and preceding physical triggers than the normal albumin group. In-hospital all-cause mortality was greater in the hypoalbuminemia group than in the normal albumin group (9.5 % vs. 1.9 %, p < 0.001). Both cardiac (3.0 % vs. 0.5 %, p = 0.015) and non-cardiac (6.5 % vs. 1.4 %, p = 0.002) mortality was greater in the hypoalbuminemia group. In multivariable logistic regression analysis, hypoalbuminemia was independently associated with increased in-hospital mortality, even after adjusting for confounders, including age, sex, and triggering events (odds ratio, 3.23; 95 % confidence interval, 1.31-7.95; p = 0.011). CONCLUSIONS: In patients with takotsubo syndrome, hypoalbuminemia is a common comorbidity and is associated with a substantial risk of in-hospital death. Close monitoring and comprehensive critical care are required in these patients.

Occurrence of late acquired peri-stent contrast staining: comparison between sirolimus-eluting stents and everolimus-eluting stents.

Peri-stent contrast staining (PSS) is an abnormal angiographic finding following drug-eluting stent implantation which suggests the presence of a space outside the stent struts. PSS has been reported to be associated with very late stent thrombosis (VLST). The aims of this study were to compare the occurrence rate of late acquired PSS between sirolimus-eluting stent (SES) and everolimus-eluting stent (EES) implantation, and to identify clinical characteristics associated with PSS. The percutaneous coronary intervention (PCI) database of our hospital was queried to identify patients meeting the following criteria: (i) patients who received SES or EES in de novo coronary artery lesions; and (ii) patients who had angiographic follow-up between 3 and 15 months after stent implantation. There were 221 patients with 249 lesions treated with SES, and 173 patients with 212 lesions treated with EES. The occurrence of PSS was evaluated and compared between SES and EES implantation on a patient and lesion basis. The occurrence rate of late acquired PSS with EES was lower than that with SES. (On a patient basis; 1.2% versus 4.5%, P = 0.045, on a lesion basis; 0.9% versus 4.0%, P = 0.043). Among the clinical characteristics, chronic total occlusion (CTO) lesions were associated with PSS. The occurrence of late acquired PSS in EES was lower than that in SES. In conclusion, the occurrence rate of late acquired PSS with EES was lower than that with SES, however, it remains to be determined whether this difference translates to the difference in the rate of VLST.

Effects of submaximal exercise on blood rheology and sympathetic nerve activity.

BACKGROUND: To explore the acute effects of submaximal exercise on blood rheology and sympathetic nerve activity. METHODS AND RESULTS: The effects of exercise (20 or 80 Watts (W)) on blood rheology and sympathetic nerve activity were assessed in 10 healthy Japanese men. Blood sampling and heart rate variability (HRV) recording were performed during 20-min supine rest and standing ergometric exercise (20 W for 10 min, 80 W for 10 min) and recovery. Blood passage time across the microchannels (diameter, 7 microm) as a parameter of blood rheology, and the number of adhesive leukocytes on microchannel terraces as a parameter of leukocyte activation were measured. Sympathetic nerve activity was evaluated by plasma noradrenalin levels and the ratio of low-frequency (LF)/high-frequency (HF) by spectral analysis of HRV. Compared with values while supine at rest, significant increases in hematocrit, leukocyte count, noradrenalin level and blood passage time were seen after strenuous ergometer exercise at 80 W (P<0.01 each). The LF/HF ratio and nitric oxide metabolites tended to be increased with 80 W exercise. CONCLUSIONS: Strenuous exercise dynamically alters blood rheological parameters, probably by changes in hematocrit and sympathetic nerve activity.

Circulating CD34+/133+ progenitor cells in patients with stable angina pectoris undergoing percutaneous coronary intervention.

BACKGROUND: This study explored the clinical significance of CD34(+)/133(+) circulating progenitor cell (CPC) counts in patients with stable angina pectoris (AP) who underwent percutaneous coronary intervention (PCI). METHODS AND RESULTS: Subjects comprised 52 patients with stable AP requiring PCI and 50 control patients without AP. In the AP group, blood samples were taken before and 20 min and 24 h after PCI to measure CPC counts by fluorescence-activated cell sorter analysis. The baseline number of CPCs was smaller in the AP group than in controls. In the AP group, body mass index (BMI) correlated positively with the baseline number of CPCs and was an independent predictor of CPC count in multivariate regression analysis. Other conventional risk factors, daily exercise activity and statin administration showed no association with CPC count. CPC counts remained unchanged within 24 h after PCI. CONCLUSIONS: CPC counts in patients with AP are influenced by BMI, but not by other coronary risk factors. CPC counts remain unchanged within 24 h after PCI.

Impact of body temperature at admission on inhospital outcomes in patients with takotsubo syndrome: insights from the Tokyo Cardiovascular Care Unit Network Registry.

BACKGROUND: Takotsubo syndrome occasionally occurs in patients with fever due to underlying diseases. However, the impact of body temperature on inhospital prognosis of patients with takotsubo syndrome remains unknown. METHODS: Using the patient cohort in the Tokyo Cardiovascular Care Unit Network Registry from 2013 to 2015, we identified 421 eligible patients whose data on body temperature at admission were available and classified them into three groups: high body temperature group (≥37.5°C; n=27), normal body temperature group (36.0-37.4°C; n=319), and low body temperature group (≤35.9°C; n=75). We compared the patient characteristics and inhospital outcomes among the three groups. RESULTS: On admission, the high body temperature group showed a higher proportion of men and preceding physical triggers, higher heart and respiratory rates, and higher C-reactive protein level than the other groups. Inhospital all-cause mortality was significantly higher in the high body temperature group than in the normal or low body temperature group (18.5% vs. 2.2% vs. 4.0%, respectively, P<0.001). Both cardiac mortality (11.1% vs. 1.3% vs. 1.3%, P=0.001) and non-cardiac mortality (7.4% vs. 0.9% vs. 2.7%, P=0.031) were also significantly higher in the high body temperature group. Multivariable logistic regression analysis showed that high body temperature (reference: normal body temperature) was significantly associated with higher inhospital mortality (adjusted odds ratio 4.22; 95% confidence interval 1.15-15.51; P=0.030). CONCLUSIONS: Our findings suggest that high body temperature at admission is a strong predictor of inhospital mortality in patients with takotsubo syndrome. Febrile takotsubo syndrome patients may need to be managed with recognition of life-threatening conditions from the time of diagnosis, no matter what the causes of fever are.

Effects of pitavastatin on fasting and postprandial endothelial function and blood rheology in patients with stable coronary artery disease.

BACKGROUND: Because postprandial hypertriglyceridemia and hyperglycemia may promote atherosclerosis, the present study investigated the effects of a clinical dose of pitavastatin on endothelial function and blood rheology in patients with coronary artery disease (CAD) before and after eating a test meal. METHODS AND RESULTS: The 16 patients with stable CAD and mild dyslipidemia and 6 age-matched healthy men as controls were recruited. In each group, forearm blood flow (FBF) was measured during postischemic reactive hyperemia and blood samples were taken before and 2 h after the test meal. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also measured. The patients were started on pitavastatin 2 mg/day. The tests were repeated after 6 months. Maximum FBF during hyperemia in the baseline fasting phase was significantly lower in CAD patients than in control subjects (P=0.040). Fasting and postprandial FBF during reactive hyperemia significantly improved after pitavastatin treatment (P<0.05 vs baseline data for each phase) associated with reduced urine 8-OHdG, increased plasma adiponectin and improved lipid profile. No significant differences in baseline rheological parameters were seen between controls and CAD patients. CONCLUSIONS: Pitavastatin significantly improved fasting and postprandial dyslipidemia and endothelial dysfunction in CAD patients, partly via reducing oxidative stress and increasing plasma adiponectin, although rheological parameters remained unchanged.

IgG4-related Pericarditis in which Oral Corticosteroid Therapy Was Effective.

IgG4-related diseases (IgG4-RDs) have recently been reported in many organs other than the salivary, pancreatic and hepatobiliary systems. A 64-year-old woman was referred to our department for her abdominal fullness and cardiomegaly on chest X-ray. After draining the pericardial fluid, her symptom promptly diminished, and pericardial friction rubbing became clearly audible. Elevated serum levels of IgG and IgG4 and ureteral wall thickening on computed tomography suggested IgG4-RD. After the initiation of oral corticosteroid therapy, the pericardial effusion was resolved, and she has been in a steady-state condition for the past two years.