Black tea increases coronary flow velocity reserve in healthy male subjects

Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.     

Effect of mental stress on coronary flow velocity reserve in healthy men

The effect of mental stress on coronary flow velocity reserve (CFVR) was examined in healthy men using transthoracic Doppler echocardiography. In the mental stress group (n = 31), CFVR was significantly reduced at 15 (to 3.3 +/- 0.8, p <0.001) and 30 (to 3.7 +/- 0.8, p <0.01) minutes after mental stress testing, compared with before mental stress (4.3 +/- 0.9), whereas it did not change in each of 3 measurements in control subjects (n = 10). Mental stress impaired coronary circulation even after a certain interval after the stress.     

The association between hematological parameters and coronary flow reserve and coronary haemorheology in healthy subjects

Studies carried out on sheep's have suggested possible effects of hematological parameters on coronary flow reserve (CFR). However, there is no study published investigating possible effects of hematological parameters and blood viscosity on coronary haemorheology and CFR in humans. We investigated the possible effects of hematological parameters on CFR using transthoracic echocardiography. METHODS: This study was conducted on 142 healthy subjects free of known cardiovascular risk factors between ages of 18-50 years. Hematological parameters were measured using an automated blood analyzer. Transthoracic echocardiographic examination including CFR measurement was performed on each subject using an Acuson Sequoia C256 Echocardiography System. RESULTS: The study group (142 subject) was divided into two according to the mean CFR values as the group with lower than mean CFR value and the group with upper than mean CFR value. Hematocrit (42.21+/-3.86 vs 40.27+/-3.97, P=0.004), LDL cholesterol, hsCRP values differed between the lower CFR and higher CFR groups. The other hematological parameters including hemoglobin value were similar between the two groups. hsCRP (beta=-0.334, P=0.001), mitral E/A ratio (beta=0.119, P=0.024), and haematocrit (beta=-0.161, P=0.064) values were the independent predictors of CFR. In women's subgroup, age, hemoglobin, hematocrit, and hsCRP values tended to differ between the lower CFR and the higher CFR subgroups. In men's subgroup systolic blood pressure, hsCRP, and mitral E velocity were different between the two groups. CONCLUSION: In addition to the coronary endothelial and coronary microvascular functions, hematocrit and blood viscosity might have some effect on coronary haemorheology and CFR.     

Experimental hyperhomocysteinemia impairs coronary flow velocity reserve

BACKGROUND: Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. One mechanism is considered to be deteriorated endothelial function that is recovered by vitamin C. However, its direct action on coronary circulation has yet to be examined. This study was designed to test the hypothesis that experimental acute hyperhomocysteinemia would impair coronary flow velocity reserve (CFR) by increasing oxidative stress. METHODS: Eleven healthy male volunteers (aged 23.3+/-0.9 years) were enrolled. CFR induced by intravenous 5'-adenosine triphosphate infusion was measured by transthoracic-Doppler echocardiography. Measurements were taken before and 4 h after administration of a placebo, oral methionine (L-methionine 0.1 g/kg) or oral methionine plus vitamin C (2 g) on 3 separate days. RESULTS: The baseline average diastolic peak velocity (APV) was similar in all 3 groups. In the methionine group, plasma homocysteine increased (12.9+/-7.0 to 32.1+/-9.4 nmol/ml, p<0.0001), while APV under hyperemic conditions (APV-hyp) and CFR significantly decreased (87.2+/-11.4 cm/sec and 4.02+/-0.70 to 73.2+/-10.2 cm/sec and 3.35+/-0.52, p=0.0022 and 0.0030, respectively). Moreover, there was a significant inverse correlation between the plasma homocysteine and CFR (r=-0.620, p=0.0021). However, upon simultaneous administration of vitamin C, APV-hyp and CVR did not decrease despite an elevation in plasma homocysteine. CONCLUSIONS: Experimentally induced acute hyperhomocysteinemia significantly decreased CFR, and this decrease was significantly reversed by vitamin C administration. Oxidative stress is suggested to play a major role in the deleterious effects of homocysteine on the coronary microcirculation.     

Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions

BACKGROUND: Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions. METHODS AND RESULTS: FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was <0.75 and CFR>or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). CONCLUSIONS: Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.     

Effect of long-term cilostazol administration on coronary flow velocity and coronary flow reserve]

Cilostazol, a novel potent inhibitor of phosphodiesterase, increases coronary flow. The effects of cilostazol on coronary flow velocity and coronary flow reserve were studied in 103 patients with coronary artery disease who underwent coronary angiography. Cilostazol 200 mg/day was administered for 3 months (31 patients) or 6 months (37 patients), and coronary flow reserve were measured before and after the cilostazol administration. Coronary flow reserve were measured twice at an interval of 6 months in the control group (35 patients). The Doppler guide wire was advanced into the coronary artery with no significant vessel stenosis. After obtaining continuous baseline coronary flow velocity, an intracoronary infusion of papaverine (10 mg) was performed to measure coronary flow reserve. There were no significant differences in coronary flow velocity just before intracoronary papaverine infusion between the initial and follow-up studies in any of the 3 groups. Coronary flow reserve increased significantly after cilostazol administration in the 3 months and 6 months groups compared with before administration (3 months group: 2.8 +/- 0.8 vs 2.4 +/- 0.9, p < 0.05; 6 months group: 2.8 +/- 1.0 vs 2.4 +/- 0.7, p < 0.01). However, there was no significant difference in coronary flow reserve in the control group between follow-up and initial studies (2.7 +/- 0.8 vs 2.5 +/- 0.8, NS). In conclusion, the long-term oral administration of cilostazol for 3 or 6 months improves coronary flow reserve.     

Coronary flow velocity reserve in hypertensive patients with left ventricular systolic dysfunction

BACKGROUND: Hypertensive microvascular disease is speculated to be a limiting factor for the ability of left ventricular (LV) hypertrophy to maintain LV systolic function in systemic hypertension. The role of coronary reserve, which may be affected by microvascular disease, remains uncertain in the pathophysiology of hypertensive heart disease. HYPOTHESIS: A progressive impairment of coronary flow velocity reserve (CFVR) according to the presence and severity of LV systolic dysfunction is anticipated to occur in hypertension. METHODS: According to the absence or presence of LV dysfunction (LV fractional shortening - FS% < 30), two groups of hypertensive patients were investigated: HP1 (n = 9, FS% = 36+/-6) and HP2 (n = 13, FS% = 18+/-6). Eight normal subjects (NL) served as controls (LVFS% = 35+/-3). Doppler blood flow velocity was obtained from the left anterior descending coronary artery using transesophageal echocardiography before, and during 6-min continuous adenosine infusion (140 microg x kg(-1) x min(-1) intravenous). The CFVR was calculated as the ratio of maximal to baseline peak diastolic flow velocities. RESULTS: The comparison among NL, HP1, and HP2 groups showed statistically different (p < 0.05) mass index (101+/-18, 172+/-46, and 257+/-54 g x m(-2)), end-systolic wall stress (76.9+/-14.4, 78.4+/-23.9, and 174.5+/-43.0 10(3) x dyn x cm(-2)), and CFVR (3.5+/-0.6, 3.2+/-0.4, and 2.6+/-0.8), respectively. The CFVR correlated significantly and directly with LVFS% (r = 0.40) and correlated inversely with both mass index (r = -0.54) and end-systolic stress (r = -0.40). CONCLUSIONS: These results indicate that CFVR impairment is weakly related to LV dysfunction in hypertension.     

Flow velocity and predictors of a suboptimal coronary flow velocity reserve after coronary balloon angioplasty.

AIMS: This study was conducted to analyse flow velocity parameters and predictors of a suboptimal coronary flow reserve (<2.5) following balloon angioplasty. METHODS: Two hundred and twenty-five patients underwent sequential intracoronary Doppler as part of the DEBATE I study. Of these, 183, with complete angiography and Doppler at the 6-month follow-up, were included. Univariate and multivariate logistic analysis was performed to identify independent predictors of post-procedural suboptimal coronary flow reserve, defined as coronary flow reserve <2.5. RESULTS: Forty-eight per cent (n=88) of the patients achieved a suboptimal coronary flow reserve. These patients had higher baseline velocities (cm.s(-1)) before balloon angioplasty (18+/-9 vs 14+/-6, P=0.004), after balloon angioplasty (22+/-11 vs 14+/-5, P<0.001) and at follow-up (19+/-9 vs 16+/-6, P=0.011) than the optimal coronary flow reserve group. Although the suboptimal group had lower hyperaemic velocities (cm.s(-1)) after balloon angioplasty than the optimal group (42+/-17 vs 49+/-16, P=0.008), these velocities became similar at follow-up. Increasing age (odds ratio, OR 1.071, P=0.0002), female gender (OR 2.52, P=0.014) and increasing pre-procedural baseline average peak velocities (OR 1.056, P<0.001) were found to be independent predictors of a suboptimal coronary flow reserve following balloon angioplasty. CONCLUSION: A suboptimal coronary flow reserve was associated with (1) a chronically elevated baseline average peak velocity (2) a transient deficit in the hyperaemic average peak velocity (3) the elderly, and female gender.     

Association between insulin resistance and reduced coronary vasoreactivity in healthy subjects

BACKGROUND: Insulin resistance appears to be an important risk factor for coronary artery disease. OBJECTIVE: To examine the role of insulin resistance on coronary vasoreactivity in healthy subjects. PATIENTS AND METHODS: Myocardial blood flow was quantitated using positron emission tomography and oxygen-15-labelled water in 10 healthy, nonobese men. The perfusion measurements were performed basally and during adenosine infusion, which has been used as a measure of coronary vasoreactivity. After perfusion measurements were taken, whole-body glucose uptake was determined using the euglycemic hyperinsulinemic clamp technique. RESULTS: Basal myocardial blood flow was 0.89+/-0.21 mL.g(-1).min(-1); adenosine significantly increased the flow to 4.00+/-1.13 mL.g(-1).min(-1). Adenosine-stimulated myocardial blood flow was inversely associated with fasting serum insulin concentration (r=-0.69, P<0.05). Concordantly, hyperemic blood flow was associated with whole-body glucose uptake during euglycemic hyperinsulinemic conditions (r=0.64, P<0.05). Basal myocardial blood flow was not affected by insulin resistance. CONCLUSION: The results of the present study demonstrate the novel finding that insulin resistance is associated with reduced coronary vasoreactivity, even in healthy subjects.     

Agreement between coronary flow velocity reserve and stress echocardiography in intermediate-severity coronary stenoses.

Visual and quantitative assessments of percent diameter stenosis on coronary angiography correlate poorly with functional testing, particularly in intermediate-severity (40%-70%) lesions, yet are frequently relied on to make decisions regarding revascularization. Coronary flow velocity reserve (CFVR) and relative CFVR (RCFVR) are promising methods for on-line functional assessment of lesion severity in the catheterization laboratory. We sought to determine the agreement between maximal, mean, and relative CFVR and stress echocardiography in intermediate-severity stenoses. The results of exercise or dobutamine stress echocardiography and CFVR measured by intracoronary Doppler were compared in 28 patients referred for assessment of intermediate-severity stenoses, using 15 patients with either angiographically normal coronary arteries or diameter stenoses > 70% as reference groups. CFVR was measured at least three times in response to a bolus of adenosine in the target vessel distal to the stenosis. RCFVR (target/normal vessel CFVR) was also measured in 27 patients. Maximal, mean (of three measures), and relative CFVR were calculated. CFVR > or = 2.0 and RCFVR > or = 0.75 were accepted as normal. A minority (29%) of patients in the intermediate-severity stenosis group had a positive test by either method. There was good to very good agreement between stress echocardiography and maximal CFVR (84%, kappa = 0.62, P < 0.0001) and RCFVR (81%, kappa = 0.59, P < 0.001) across the entire patient cohort, though in the intermediate subgroup concordance was only fair. Using the mean (of three measures of) CFVR for the same comparison improved the agreement in the intermediate subgroup to good (86%, kappa = 0.58, P = 0.002), and in the entire cohort the agreement was very good (88%, kappa = 0.74, P < 0.0001). There was only fair correlation between measures of CFVR and percent coronary stenosis. CFVR improved from 1.8 +/- 0.8 to 2.7 +/- 0.7 after percutaneous intervention (n = 12, P < 0.0001). These results suggest that there is good agreement between CFVR and stress echocardiography across a wide range of coronary lesion severity. The mean of three CFVR measurements distal to the target vessel stenosis increases diagnostic accuracy. Intracoronary Doppler flow velocity measurements at the time of cardiac catheterization may facilitate improved decision-making by providing the ability to assess the functional significance of coronary stenoses on-line.     

Corrected coronary flow velocity reserve: a new concept for assessing coronary perfusion

OBJECTIVES

In order to limit the variability of coronary flow velocity reserve (CFVR), we analyzed which factors independently affect CFVR and established a new parameter integrating these factors.

BACKGROUND

Coronary flow velocity reserve (CFVR) is a frequently used parameter for evaluating the physiological significance of epicardial stenosis and microvascular function. Since CFVR measurements are done in substantially different hemodynamic and clinical situations, interpretation of CFVR requires correction for major influencing factors.

METHODS

In 141 patients with angina-like symptoms and angiographically unobstructed coronary arteries, intracoronary Doppler measurements were performed in at least two coronary vessels. Coronary flow velocity reserve was calculated as the ratio of hyperemic average peak velocity (hAPV), after intracoronary bolus of adenosine, to baseline average peak velocity (bAPV).

RESULTS

Analysis of covariance revealed that only bAPV (p < 0.0001) and age (p < 0.0001) were independent factors influencing CFVR. Based on a regression model for estimation of predicted CFVR values, individual CFVR values (CFVR_ind) obtained at different bAPV and age were transformed in corrected CFVR values (CFVR_corr) by relating them to a mean bAPV of 15 cm/s and a mean age of 55 years. The transformation from CFVR_ind into CFVR_corr for the left anterior descending artery can be done by using the following equation: CFVR_corr = 2.85*CFVR_ind*10 ^{0.48*log(bAPV) + 0.0025*age − 1.16}. When applying this new parameter to conditions assumed to cause microvascular dysfunction, analysis showed that only patients with diabetes showed a significant decrease of traditional CFVR and CFVR_corr, whereas a history of hypertension and current smoking habit had no influence on CFVR_corr.

CONCLUSIONS

The concept of CFVR_corr standardizes CFVR for bAPV and age as the major physiological determinants. Especially in patients with microvascular dysfunction, this approach may help to discriminate between conditions directly affecting vasodilator reserve and conditions primarily affecting bAPV.     

Measurement of coronary flow velocity with Doppler catheter: evaluation of coronary flow reserve in successful angioplasty

To assess the therapeutic effect of percutaneous transluminal coronary angioplasty (PTCA) on coronary flow reserve, coronary flow velocity (CFV) was measured with a Doppler catheter before and immediately after PTCA in 11 patients, who underwent elective PTCA for critical stenosis in proximal or mid portion of the left anterior descending artery (LAD). A Doppler catheter was positioned at the proximal portion of the LAD and the CFV was measured at rest and after intracoronary injection of 6 ml of contrast material (Iopamidol), 6 ml of saline or 3 mg of Isosorbide Dinitrate (ISDN). Peak to resting velocity ratio (PRVR) was calculated as an estimate of coronary flow reserve. Percent diameter stenosis (%S) was measured from cineangiogram. A translesional pressure gradient was obtained with an angioplasty catheter. These parameters measured in PTCA candidates were compared with those in 11 patients whose LAD had no critical stenosis. After PTCA, %S was decreased (94.2 +/- 1.4 vs 34.1 +/- 5.1%; mean +/- SEM). Pressure gradient was also decreased (59.5 +/- 4.9 vs. 25.1 +/- 3.3 mmHg). There was no difference between mean CFV at rest in patients before PTCA and that in patients without stenosis (4.52 +/- 0.63 vs. 5.46 +/- 0.61 cm/sec). By successful PTCA, CFV at rest was increased (7.39 +/- 1.32, p less than 0.05 vs. before PTCA). PRVRs in patients before PTCA were smaller than those in patients without stenosis (1.5 +/- 0.1, 1.4 +/- 0.1, 1.6 +/- 0.2 vs. 2.8 +/- 0.1, 2.5 +/- 0.2, 2.8 +/- 0.2, p less than 0.01; by contrast material, saline, ISDN, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Multifactorial determinants of reduced coronary flow reserve after dipyridamole in dilated cardiomyopathy

Coronary sinus blood flow (ml/100 g left ventricular [LV] mass/min) and coronary resistance (mean aortic minus LV mean diastolic pressures/coronary sinus blood flow, mm Hg/[ml/100 g/min]) were studied in 7 control patients and in 11 patients with severe dilated cardiomyopathy (DC) and normal coronary arteriograms. Basal coronary sinus blood flow was not different in the 2 groups. After intravenous administration of dipyridamole (0.14 mg/kg/min X 4 min), coronary sinus blood flow and dipyridamole/basal coronary sinus blood flow ratio were significantly (p less than 0.001) lower in the DC group than in the normal group (coronary sinus blood flow 188 +/- 48 vs 408 +/- 58, respectively; blood flow ratio 1.78 +/- 0.35 vs 4.01 +/- 0.56, respectively), and the coronary resistance was higher in the DC group than in the control group (0.39 +/- 0.15 vs 0.22 +/- 0.03, respectively, p less than 0.01). After administration of dipyridamole in patients with DC, no correlation could be found between coronary sinus blood flow and LV mean diastolic, mean aortic or coronary driving pressures, i.e., mean aortic minus LV mean diastolic pressures. Thus, in DC patients, neither an elevated LV diastolic pressure nor a low coronary perfusion pressure can totally account for the restriction of the coronary flow reserve after dipyridamole.     

Abnormal coronary vasomotion during exercise in patients with normal coronary arteries and reduced coronary flow reserve

A reduced coronary flow reserve has been reported in patients with ischemialike symptoms and normal coronary arteries. In 13 such patients, both coronary vasomotion and flow reserve were studied. The luminal area of the proximal and distal third of the left anterior descending and left circumflex artery were determined by biplane quantitative coronary arteriography using a computer-assisted system. Patients were studied at rest, during submaximal supine bicycle exercise (4.0 minutes, 116 W), and 5 minutes after sublingual administration of 1.6 mg nitroglycerin. Heart rate, mean pulmonary pressure, and mean aortic pressure as well as the percent change of both proximal and distal luminal area were determined. In 10 of the 13 patients, coronary sinus blood flow was measured by coronary sinus thermodilution technique at rest and after dipyridamole infusion (0.5 mg/kg in 15 minutes) 10 +/- 5 days after quantitative coronary arteriography. Coronary flow ratio (dipyridamole/rest) and coronary resistance ratio (rest/dipyridamole) were determined in these patients. Patients were divided into two groups according to the behavior of the coronary vessels during exercise (vasodilation, group 1; vasoconstriction, group 2). Coronary vasodilation of the proximal (luminal area +26%, p less than 0.001) and distal (+45%, p less than 0.001) artery was observed in seven patients (group 1) during exercise and after sublingual nitroglycerin (+46%, p less than 0.001; and +99%, p less than 0.001, respectively). In group 2 (n = 6), however, there was coronary vasoconstriction of the distal vessel segments (-24%, p less than 0.001) during exercise, whereas the proximal coronary artery showed vasodilation (+26%, p less than 0.001) during exercise. After sublingual nitroglycerin, both vessel segments elicited vasodilation (distal coronary, +44%, p less than 0.001; proximal coronary artery, +47%, p less than 0.001). Coronary flow ratio amounted to 2.5 in group 1 and 1.2 in group 2 (p less than 0.05) and coronary resistance ratio to 2.7 in group 1 and to 1.2 in group 2 (p less than 0.05), respectively. Thus, among patients with ischemialike symptoms and normal coronary arteries, there is a group of patients (group 2) with an abnormal dilator response of the distal coronary arteries to the physiologic dilator stimulus of exercise and a reduced dilator capacity of the resistance vessels after dipyridamole (abnormal coronary vasodilator syndrome). The nature of this exercise-induced distal coronary vasoconstriction is not clear but might be due to an abnormal neurohumoral tone that may cause or contribute to the blunted vascular response during exercise.