Takuro Takumi

Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = −0.24, P < 0.05; r = −0.17, P < 0.05, r = −0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.

Relationship between hyperglycemia and coronary vascular resistance in non-diabetic patients

BACKGROUND Hyperglycemia upon hospital admission in patients with acute myocardial infarction is associated with the no-reflow phenomenon after successful reperfusion, and increased mortality. However, the mechanism underlying this phenomenon remains unclear. Therefore, the aim of this study was to characterize coronary hemodynamics in a homogenous group of non-diabetic patients without coronary artery disease. METHODS AND RESULTS A total of 104 consecutive non-diabetic patients (mean age, 62+/-14 years) without coronary artery disease underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined by intra-coronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Coronary vascular resistance (CVR) was calculated as the mean arterial pressure divided by coronary blood flow (CBF). Baseline CVR was shown as CVR at control and minimal CVR was shown as CVR with papaverine administration. Fasting plasma glucose (FPG) level had a significant, positive correlation with baseline CVR and minimal CVR (r=0.24, p<0.02 and r=0.21, p<0.05, respectively). Hemoglobin A1c (HbA1c) also had a significant, positive correlation with baseline CVR and minimal CVR (r=0.31, p<0.01 and r=0.32, p<0.01, respectively). The percent change in CBF induced by Ach was inversely correlated with HbA1c but not with FPG (r=0.22, p<0.05 and r=0.06, p=0.57, respectively). By contrast, neither FPG nor HbA1c had significant correlation with coronary flow reserve to papaverine. CONCLUSION These data demonstrate that elevated glucose levels are associated with increases in baseline and minimal coronary vascular resistance. These changes may contribute to unfavorable coronary hemodynamics in non-diabetic patients without coronary heart disease.

Enjoying hobbies is related to desirable cardiovascular effects

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 ± 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% ± 77% vs 25% ± 37%, P < 0.05, 4% ± 13% vs −3% ± 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

Angiotensin-Converting Enzyme Inhibitor Prevents the Worsening of Renal Function in the Late Phase after Percutaneous Coronary Intervention.

AIM The amount of contrast media and renal atheroemboli are risk factors for acute kidney injury after percutaneous coronary intervention (PCI). However, the chronic kidney injury after PCI has not been fully characterized. The purpose of this study was to investigate factors affecting renal function in the late phase after PCI by measuring serum Cystatin C (CysC). METHODS In 143 consecutive patients who underwent elective PCI, CysC was evaluated at baseline and at 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association between %CysC and baseline characteristics, including medication use, was assessed. RESULTS Of 143 patients, 86 had worsening renal function (WRF; %CysC ≥0), and 57 did not (non-WRF; %CysC <0). Only the use of angiotensin-converting enzyme inhibitor (ACEI) and baseline CysC were significantly different between WRF and non-WRF patients (15 vs. 40%, p=0.001 and 1.02±0.26 vs. 1.13±0.26 mg/L, p=0.015). In univariate analysis, the use of ACEI and CysC were negatively associated with WRF [Odds ratio (OR)=0.26, 95% confidence interval (CI)=0.12-0.57, p<0.001 and OR=0.20, 95% CI=0.05-0.73, p=0.015]. Furthermore, multivariate analysis revealed that the use of ACEI and CysC significantly correlated with WRF (OR=0.26, 95% CI=0.11-0.57, p<0.001 and OR=0.20, 95% CI=0.05-0.74, p=0.016). The %CysC in 36 patients with ACEI was significantly lower than that in 107 patients without ACEI [median: -3.8%; interquartile range (IQR), -11.0 to 4.2%; vs. median: 3.3%; IQR -2.9 to 11.0%, p=0.001]. CONCLUSION The use of ACEI was associated with lower CysC after PCI, suggesting that ACEI prevents worsening of renal function in late phase after PCI.

Prospective Study on the Incidence of Cerebrovascular Disease After Coronary Angiography

Aim: Previous studies have reported a 10.2%–22% rate of silent cerebral infarction and a 0.1% –1% rate of symptomatic cerebral infarction after coronary angiography (CAG). However, the risk factors of cerebral infarction after CAG have not been fully elucidated. For this reason, we investigated the incidence and risk factors of CVD complications within 48 h after CAG using magnetic resonance imaging (MRI) (Diffusion-weighted MRI) at Kagoshima University Hospital. Methods: From September 2013 to April 2015, we examined the incidence and risk factors, including procedural data and patients characteristics, of cerebrovascular disease after CAG in consecutive 61 patients who underwent CAG and MRI in our hospital. Results: Silent cerebral infarction after CAG was observed in 6 cases (9.8%), and they should not show any neurological symptoms of cerebral infarction. Only prior coronary artery bypass grafting (CABG) was more frequently found in the stroke group (n = 6) than that in the non-stroke group (n = 55); however, no significant difference was observed (P = 0.07). After adjusting for confounders, prior CABG was a significant independent risk factor for the incidence of stroke after CAG (odds ratio: 11.7, 95% confidence interval: 1.14–129.8, P = 0.04). Conclusions: We suggested that the incidence of cerebral infarction after CAG was not related to the catheterization procedure per se but may be caused by atherosclerosis with CABG.

Validity of a Novel Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Cardiovascular Disease Patients Treated with Statins

Aim: The Friedewald equation is the standard method for estimating low-density lipoprotein cholesterol (LDL-C) levels [LDL-C(F)] and fixes the ratio of triglyceride (TG) to very LDL-C at 5. However, this has been reported to underestimate LDL-C, particularly in patients with LDL-C < 70 mg/dL. A novel method for LDL-C estimation [LDL-C(M)] using an adjustable factor instead of a fixed value of 5 has recently been proposed. The purpose of this study was to validate LDL-C(M) in Japanese patients with cardiovascular disease (CVD) treated with statins. Methods: In 385 consecutive CVD patients treated with statins, LDL-C(M) and LDL-C(F) levels were compared with directly measured LDL-C [LDL-C(D)]. Results: Mean LDL-C(D), LDL-C(F), and LDL-C(M) were 81.7 ± 25.5, 76.4 ± 24.6, and 79.9 ± 24.5 mg/dL, respectively. In all patients, both LDL-C(F) and LDL-C(M) were significantly correlated with LDL-C(D) [LDL-C(F) vs. LDL-C(D): R = 0.974, p < 0.001; LDL-C(M) vs. LDL-C(D): R = 0.987, p < 0.001]. In patients with LDL-C(D) < 70 mg/dL, LDL-C(M) showed a better correlation with LDL-C(D) compared with LDL-C(F) [LDL-C(M) vs. LDL-C(D): R = 0.935, p < 0.001; LDL-C(F) vs. LDL-C(D): R = 0.868, p < 0.001]. In contrast, the correlation of LDL-C(D) with LDL-C(M) or LDL-C(F) was similar in patients with LDL-C(D) ≥ 70 mg/dL. Conclusions: In Japanese patients with CVD treated with statins, LDL-C level estimated by this novel method might be more accurate than those estimated using the Friedewald equation for LDL-C levels < 70 mg/dL.

ASSOCIATION OF SERUM CONCENTRATION OF BILIRUBIN WITH CORONARY ENDOTHELIAL FUNCTION; THE RELATIONSHIP BETWEEN BILIRUBIN AND OXIDATIVE STRESS, INFLAMMATORY MEDIATOR AND LIPID/GLUCOSE METABOLISM

Methods: The study population consisted of 141 patients without CHD underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of acetylcholine (Ach) and nitroglycerin (NTG) using a Doppler guidewire. Coronary endothelial function was evaluated by the response of coronary blood flow (CBF) and coronary artery diameter (CAD) to Ach. Serum bilirubin, Malondialdehyde-modified LDL (MDA-LDL), high sensitive C-reactive protein (hs-CRP), LDL-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), fasting plasma glucose (FPG) and immuno-reactive insulin (IRI) were also measured. Homeostasis model assessment insulin resistance index (HOMA-R) and estimated glomerular filtration rate (eGFR) were calculated.