Akiko Yoshikawa

Atrial fibrillation-induced endothelial dysfunction improves after restoration of sinus rhythm

BACKGROUND Recent evidence suggests that atrial fibrillation (AF) adversely affects endothelial function. The goal of this study was to assess endothelial function in patients with AF before and after restoration of sinus rhythm by catheter ablation (ABL). METHODS Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were conducted with Endo-PAT2000 (Itamar Medical, Caesarea, Israel) in 27 patients with persistent AF before ABL and in 21 control subjects with sinus rhythm (SR). According to cardiac rhythm on the morning after ABL, patients were divided into two groups: day 1-restored SR group (n=19) and day 1-recurred AF group (n=8). Based on the cardiac rhythm at 6 months after ABL, the restored SR group was further subdivided into the month 6-maintained SR group (n=11) and the month 6-recurred AF group (n=6). RESULTS Loge RH-PAT index (RHI) was significantly lower in the persistent AF group than in the control (SR) group (0.52 ± 0.20; 0.69 ± 0.24, p<0.01). Multivariate logistic regression analysis revealed that persistent AF was the only independent predictor of impaired endothelial function defined as loge RHI<0.6 (odds ratio, 4.96; 95% CI, 1.2 to 21.3; p<0.05). Loge RHI was significantly higher after ABL than before ABL (0.53±0.20; 0.73 ± 0.25; p<0.01) in the day 1-restored SR group. Loge RHI of the month 6-maintained SR group was comparable to that of the day 1-restored SR group. CONCLUSIONS These results suggest that AF is associated with impairment of endothelial dysfunction and that this impairment is reversed by restoration of sinus rhythm.

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.

Association of coronary shear stress with endothelial function and vascular remodeling in patients with normal or mildly diseased coronary arteries

BackgroundThe relationship between coronary remodeling, shear stress and endothelial function remains unclear. ObjectiveThe present study investigated the effects of mechanical factors on structure and function of epicardial coronary arteries. MethodsPatients (group 1: %area stenosis<40%, n=55; or group 2: %area stenosis ≥40%, n=17) with a discrete mildly stenotic lesion (%diameter stenosis<30%) underwent intravascular ultrasound examination of the left anterior descending coronary artery for determination of vessel area, lumen area, plaque area, cross-sectional areas at reference segments, and remodeling index (the ratio of vessel area at the culprit lesion to vessel area at the proximal reference site). Further, vascular reactivity was examined using intracoronary administration of acetylcholine, papaverine, and nitroglycerin. ResultsVessel area significantly correlated with plaque area in both groups (r=0.65, P<0.0001 and r=0.85, P<0.0001). Group 1 showed significantly greater acetylcholine-induced percentage changes in coronary blood flow (67±70 vs. 16±75%, P<0.05) and coronary artery diameter (−7±18 vs.−32±31%, P<0.01) and also significantly smaller coronary wall shear stress (65±27 vs. 81±32 dynes/cm2, P<0.05) than group 2. The percentage increase in coronary blood flow induced by acetylcholine was significantly and positively correlated with remodeling index in group 1 (r=0.64, P<0.0001) but not in group 2 (r=−0.03, P=0.90) and was also significantly and positively correlated with coronary wall shear stress in group 1 (r=0.46, P<0.001) but not in group 2 (r=−0.33, P=0.19). ConclusionsEndothelium-dependent vasodilation in the resistance coronary artery correlates with remodeling via increased wall shear stress when target lesions %area stenosis is <40%.

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.

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.

BRACHIAL-ANKLE PULSE WAVE VELOCITY CORRELATED WITH AN ENDOTHELIUM-INDEPENDENT VASODILATION IN CONDUIT CORONARY ARTERY

Methods: Seventy-one consecutive patients (49 men, 22 women, mean age 61±13 years) with normal or mildly diseased coronary arteries were enrolled. Vascular reactivity was assessed by intracoronary administration of papaverine, acetylcholine, and nitroglycerin using a Doppler guidewire. A bolus of papaverine induces an endothelium-independent vasodilator in resistance coronary arteries, infusion of acetylcholine induces an endothelium-dependent vasodilator in resistance and conduit coronary arteries, and a bolus of nitroglycerin induces an endothelium-independent vasodilator in conduit coronary arteries. BaPWV was measured using automated device.