Thomas Suter

Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries.

BackgroundIt has been shown that there is impairment of the vasodilatory response to acetylcholine in patients with hypercholesterolemia and angiographically normal coronary arteries. Moreover, in patients with angiographically smooth coronary arteries, the number of coronary risk factors is associated with a loss of endothelium-dependent vasodilation. The purpose of the present analysis was to evaluate in patients with and without coronary artery disease coronary vasomotor response to dynamic exercise in angiographically normal and stenosed coronary arteries and to relate the response to serum cholesterol levels as well as to other coronary risk factors. Methods and ResultsLuminal area change during exercise (delta-ex, percent change compared with rest=100%) was determined by biplane quantitative coronary arteriography in three groups: Group 1 consisted of 14 patients with normal total serum cholesterol of <200 mg/100 mL; mean, 173 mg/100 mL (mean age, 51 years). Group 2 comprised 23 patients with a slightly elevated cholesterol of 200 to 250 mg/100 mL; mean, 223 mg/100 mL (mean age, 53 years). Group 3 had 24 patients with markedly elevated cholesterol of >250 mg/100 mL; mean, 288 mg/100 mL (mean age, 54 years). Serum cholesterol levels and categorical risk factors such as positive family history, history of hypertension, smoking, obesity, and diabetes were related to exercise-induced vasomotor response. The three groups did not differ with regard to clinical characteristics, exercise work load, and hemodynamic data measured during exercise. However, delta-ex in normal vessels was significantly different between all three groups (ANOVA, P<.01): +31% (group 1), +18% (group 2), and +4% (group 3). Delta-ex in stenotic vessels did not differ between the groups: −5% (group 1), −13% (group 2), and −12% (group 3). Delta-ex of the nonstenosed vessel correlated significantly and inversely with total cholesterol, with low-density lipoprotein cholesterol, with the ratio of total to high-density lipoprotein cholesterol, and with the number of coronary risk factors present in a patient. High total cholesterol and a history of hypertension were independent risk factors for impaired coronary vasomotion. ConclusionsIn patients with and without coronary artery disease, hypercholesterolemia and a history of hypertension independently impair exercise-induced coronary vasodilation in angiographically normal coronary arteries. In the stenotic vessel, vasomotion during exercise does not appear to be influenced by the actual serum cholesterol. The precise mechanism by which the impaired vasomotion of the angiographically normal coronary arteries is mediated is unknown, but a direct negative effect of hypercholesterolemia on endothelial function or early undetected atherosclerosis appears to be the most likely explanation.

Normalization of Abnormal Coronary Vasomotion by Calcium Antagonists in Patients With Hypertension

BACKGROUND Endothelial dysfunction with a loss of endothelium-dependent vasodilation has been reported in patients with arterial hypertension. The purpose of the present study was to evaluate coronary vasomotor response to dynamic exercise in patients with coronary artery disease with and without arterial hypertension and to determine the effect of calcium antagonists on coronary vasomotion. METHODS AND RESULTS Cross-sectional areas of a normal and a stenotic coronary vessel segment were examined in 79 patients with coronary artery disease at rest and during supine bicycle exercise (Ex). Change in luminal area after acute administration of a calcium antagonist (diltiazem or nicardipine), during exercise, and after sublingual nitroglycerin (percent change compared with rest = 100%) was assessed by biplane quantitative coronary arteriography. Patients were divided into two groups: Group 1 (control) consisted of 48 patients without (normotensive subjects, n = 30; hypertensive subjects, n = 18) and group 2 of 31 patients with (normotensive subjects, n = 15; hypertensive subjects, n = 16) pretreatment with a calcium antagonist immediately before exercise. The groups did not differ with regard to clinical characteristics or hemodynamic data measured during exercise. Mean aortic pressure at rest, however, was significantly increased in hypertensive patients compared with normotensive subjects in group 1 (103 mm Hg versus 92 mm Hg, P < .01) and group 2 (110 mm Hg versus 98 mm Hg, P < .025). In group 1, exercise-induced vasomotor response was significantly different between normotensive and hypertensive patients in normal (+20% versus +1%, P < .003) and stenotic vessels (-5% versus -20%, P < .025). However, in group 2 there was coronary vasodilation in normotensive and hypertensive patients for both normal (delta Ex +23% versus +21%, P = NS) and stenotic vessel segments (+24% versus +26%, P = NS). CONCLUSIONS Abnormal coronary vasomotion during exercise can be observed in hypertensive patients with reduced vasodilator response in normal arteries and enhanced vasoconstrictor response in stenotic arteries. Calcium antagonists prevent the abnormal response of normal and stenotic coronary arteries to exercise in hypertensive patients and thus may compensate for endothelial dysfunction with reduced vasodilator response to exercise.

Validation of a new automatic system for biplane quantitative coronary arteriography

SummaryIn a collaboration between the University of Texas (software) and the University of Zürich (hardware) a compact, automatic system for biplane quantitative coronary arteriography was developed. The system is based on a 35 mm filmprojector, a slow-scan CCD-camera (image digitizing) and a computer workstation (Apollo DN 3000, image storage and processing). A new calibration procedure based on two fixed reference points in the center of the image intensifier was used (isocenter technique). Contour detection of coronary arteries was carried out in biplane projection using a geometric-densitometric edge-detection algorithm. The proximal and distal luminal areas, as well as the minimal luminal area of the stenotic vessel segment were determined.Accuracy and precision were determined from precision drilled holes in a plexiglas cube which were filled with 50%, 75% and 100% contrast medium. The diameter of the holes ranged from 0.5 to 5.0 mm. The mean difference and the standard deviation of the differences between the true and the measured diameters were 0.12 ± 0.14 mm for plane A and 0.26 ± 0.17 mm for plane B, respectively. After a second order correction the mean difference amounted to 0.02 ± 0.09 mm for plane A and 0.02 ± 0.12 mm for plane B, respectively.Intra- and interobserver variability were evaluated in 5 patients (age 60 ± 10 years) with coronary artery disease using 16 normal and 5 stenotic vessel segments (cross-sectional area ranging from 0.8 to 8.7 mm2). Two independent observers analyzed the same vessel segment twice. Intraobserver variability expressed as the standard error of estimate in percent of the mean angiographic vessel area (SEE) amounted to 2.1% for observer 1 and 4.4% for observer 2, respectively. Interobserver variability expressed as SEE was 4.1% for measurement 1 and 3.6% for measurement 2, respectively.

Exercise-induced vasomotion of angiographically normal and stenotic coronary arteries improves after cholesterol-lowering drug therapy with bezafibrate

OBJECTIVES We attempted to determine whether the coronary vasomotor response to exercise improves after cholesterol-lowering drug therapy with bezafibrate. BACKGROUND Hypercholesterolemia and other coronary risk factors are associated with impaired endothelium-dependent coronary vasomotor response to physiologic or pharmacologic stimuli, even in the absence of overt coronary atherosclerosis. It is still unknown whether the coronary artery vasomotor response to dynamic exercise improves under cholesterol-lowering drug therapy. METHODS Of 15 male patients (age 51 +/- 7 years [mean +/- SD]) included in the study, 7 had markedly elevated cholesterol levels (> or = 6.5 mmol/liter, therapy group), and 8 had normal or slightly elevated cholesterol levels (< 6.5 mmol/liter, control group). At baseline and after 7 months of cholesterol-lowering therapy with bezafibrate (400 mg/day) in the therapy group, coronary vasomotor response to dynamic exercise (percent change in cross-sectional vascular area at maximal exercise vs. rest [100%]) in normal and stenotic, previously dilated vessels was assessed by quantitative coronary angiography. RESULTS During follow-up, total serum cholesterol levels in the therapy group decreased from 7.8 +/- 1.1 to 5.8 +/- 1.1 mmol/liter (p = 0.0001) and did not change significantly in the control group (from 5.4 +/- 0.9 to 6.0 +/- 1.2 mmol/liter, p = NS). Exercise-induced vasomotor response (at similar work loads in the therapy and control groups) in both normal and dilated stenotic coronary arteries improved significantly in the therapy group, from 100 +/- 9% to 109 +/- 7% (p = 0.0001, cross-sectional area at rest 100%) and from 80 +/- 11% to 106 +/- 7% (p = 0.0002), respectively, but did not improve during follow-up in the control group. CONCLUSIONS The present study indicates that cholesterol-lowering drug therapy with bezafibrate for 7 months improves exercise-induced vasomotion of angiographically normal coronary arteries. Seven months after coronary angioplasty, the reduction in serum cholesterol levels is, at least in part, associated with a restoration of the initially disturbed vasomotor response of stenotic vessel segments to exercise.

Effect of intravenous propranolol on coronary vasomotion at rest and during dynamic exercise in patients with coronary artery disease.

Coronary vasomotion was studied at rest and during bicycle exercise with biplane quantitative coronary arteriography in 28 patients with coronary artery disease. Patients were divided into two groups; the first 18 patients served as controls (group 1), and the next 10 patients were treated with propranolol 0.1 mg/kg, which was infused intravenously before exercise (group 2). Luminal area of a normal and a stenotic vessel segment was determined at rest, during supine bicycle exercise, and 5 minutes after sublingual administration of 1.6 mg nitroglycerin after exercise. In group 1, the normal vessel showed vasodilation (+16%, p less than 0.001) during exercise, whereas the stenotic vessel segment showed vasoconstriction (-31%, p less than 0.001). After sublingual administration of nitroglycerin, there was coronary vasodilation of both normal (+36%, p less than 0.001 vs. rest) and stenotic (+20%, p less than 0.001) vessel segments. Patients with angina pectoris during supine exercise (n = 10) had significantly (p less than 0.05) more vasoconstriction (-36%) than patients without angina (-23%). In group 2, intravenous administration of propranolol at rest was associated with a decrease in luminal area of both normal (-24%, p less than 0.001) and stenotic (-43%, p less than 0.001) vessel segments; however, during subsequent exercise, both normal (-2%, p = NS vs. rest) and stenotic (-3%, p = NS vs. rest) vessel segments dilated when compared with the measurements after propranolol. Administration of nitroglycerin further increased luminal area of both vessel segments (normal segment, +23%, p less than 0.001; stenotic segment, +46%, p less than 0.001 vs. rest). It is concluded that dynamic exercise in patients with coronary artery disease is associated with coronary vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Patients with exercise-induced angina had significantly more stenosis vasoconstriction than patients without angina although minimal luminal area at rest was similar. Intravenous administration of propranolol is accompanied by a significant decrease in coronary luminal area of both normal and stenotic vessel segments at rest, which is overridden by dynamic exercise and sublingual nitroglycerin. The reduction in myocardial oxygen consumption and the prevention of exercise-induced stenosis vasoconstriction might explain the beneficial effect of beta-blocker treatment in most patients with coronary artery disease.

Normalization of coronary vasomotion after percutaneous transluminal coronary angioplasty

BackgroundCoronary vasomotion was evaluated at rest and during bicycle exercise in 33 patients (age, 53±7 years) with coronary artery disease. In a first group of patients (n = 15), vasomotion was studied before and 4.3±2.3 months (early) after percutaneous transluminal coronary angioplasty (PTCA), whereas in a second group (n = 18), exercise coronary arteriography was performed 30±11 months (late) after successful PTCA. Patients with restenosis (percent area stenosis ≥75% or percent diameter stenosis ≥50%) were excluded. Methods and ResultsLuminal areas of a normal segment and the stenotic segment were determined at rest, during supine bicycle exercise, and 5 minutes after sublingual nitrate administration by using biplane quantitative coronary arteriography. Work loads before and early after PTCA were identical in group 1 and similar late after PTCA in group 2. Percent area stenosis decreased from 86% to 36% (p < 0.001) in group 1 and from 93% to 46% (p < 0.001) in group 2. Normal coronary arteries showed mild vasodilation during exercise before (+3%, NS versus rest), early (+7%, NS versus rest), and late after (+10%, p < 0.05 versus rest) PTCA. Administration of sublingual nitrate was associated with significant vasodilation of the normal vessel segment before (+27%, p < 0.001 versus rest), early (+31%, p < 0.001 versus rest), and late (+21%, p < 0.001 versus rest) after PTCA. In contrast, the stenotic vessel segments showed coronary vasoconstriction during exercise before PTCA (-25%, p < 0.001 versus rest), whereas minimal vasomotion was observed early (+2%; NS versus rest) as well as late (+5%; NS versus rest) after PTCA. Individual post-PTCA (early and late) exercise data elicited vasodilation in 19, no vasomotion in four, and vasoconstriction in 10 instances. Sublingual administration of nitrate was associated with a significant increase in minimal luminal area before (+ 18%, p < 0.05 versus rest), early (+24%, p < 0.01 versus rest), and late (+16%, p < 0.001 versus rest) after PTCA. An inverse linear correlation was found between the percent change in minimal luminal area during peak exercise and percent area stenosis at rest (r = 0.77, p < 0.001) ConclusionsExercise-induced stenosis narrowing is observed before PTCA but normal vasomotion is reestablished in two thirds of all patients early and late after PTCA. In one third, an abnormal reaction to exercise (i.e., vasoconstriction) persisted after PTCA, mainly in those patients with a residual area stenosis of 50% (percent diameter stenosis of 30%) or more. Thus, PTCA appears to have a salutary effect on coronary vasomotion during exercise, which, however, remains dependent on the severity of the residual stenosis.

Abnormal Coronary Vasomotion in Hypertension: Role of Coronary Artery Disease

OBJECTIVES This study sought to evaluate the effect of dynamic exercise on coronary vasomotion in hypertensive patients in the presence and absence of coronary artery disease. BACKGROUND Endothelial dysfunction with abnormal coronary vasodilation in response to acetylcholine has been reported in patients with arterial hypertension. METHODS Coronary artery dimensions of a normal and stenotic vessel segment were determined in 64 patients by biplane quantitative coronary arteriography at rest and during supine bicycle exercise. Patients were classified into two groups: 20 patients without evidence of coronary artery disease (10 normotensive, 10 hypertensive [group 1]) and 44 patients with coronary artery disease (26 normotensive, 18 hypertensive [group 2]). Both groups were comparable with regard to clinical characteristics, serum cholesterol levels, body mass index, exercise capacity and hemodynamic data. RESULTS Mean aortic pressure was significantly higher in hypertensive than normotensive patients. Exercise-induced vasodilation of the normal vessel segment was similar in normotensive and hypertensive patients without coronary artery disease (group 1), namely, +19% versus +20%. However, in hypertensive patients with coronary artery disease, exercise-induced vasodilation was significantly less in both normal and stenotic vessel segments than in normotensive subjects (+1% vs. +20% for normal [p < 0.003] and -20% vs. -5% for stenotic vessels [p < 0.025]). Administration of 1.6 mg of sublingual nitroglycerin at the end of exercise led to a normalization of the vasodilator response in normotensive as well as hypertensive patients. However, this response became progressively abnormal in group 2 when coronary artery disease was present. CONCLUSIONS In the absence of coronary artery disease, the vasomotor response to exercise is normal in both normotensive and hypertensive patients. However, in hypertensive patients with coronary artery disease, an abnormal response of the coronary vessels can be observed, with a reduced vasodilator response to exercise in normal arteries but an enhanced vasoconstrictor response in stenotic arteries. This behavior of the epicardial vessels during exercise suggests the occurrence of endothelial dysfunction (i.e., functional defect) that is not evident in the absence of coronary artery disease. Nitroglycerin reverses impaired coronary vasodilation, but this effect is blunted in the presence of coronary artery disease (i.e., structural defect).

Percutaneous Transluminal Coronary Angioplasty Reverses Vasoconstriction of Stenotic Coronary Arteries in Hypertensive Patients

BACKGROUND Endothelial dysfunction of coronary arteries with impaired vasodilation has been reported in patients with arterial hypertension. However, the effect of dynamic exercise on coronary vasomotion of a stenotic vessel segment before and after PTCA has not yet been evaluated in these patients. METHODS AND RESULTS Coronary vasomotion of a normal and a stenotic vessel segment was studied in 39 patients with coronary artery disease during supine bicycle exercise before and 9+/-3 months after PTCA. Luminal area changes were determined by biplane quantitative coronary arteriography. There were 21 normotensive and 18 hypertensive patients who did not differ with regard to clinical characteristics. Percent area stenosis decreased after PTCA from 90% to 39% (P<0.001) in normotensive and from 86% to 33% (P<0.001) in hypertensive patients. Exercise-induced vasomotion of the normal vessel segment was significantly different between normotensives and hypertensives before (+19% versus +1%, P<0.01) and after (+16% versus +3%, P<0.01) PTCA. In contrast, stenotic vessel segments showed vasoconstriction in both normotensive and hypertensive patients (Deltaexercise, -11% versus - 20%, P=NS), which was reversed after PTCA (+3% versus +2%, P=NS). CONCLUSIONS Normal coronary arteries show reduced vasodilation during exercise in hypertensive patients that may be explained by the presence of endothelial dysfunction. Stenotic vessels demonstrate paradoxical vasoconstriction during exercise in both normotensive and hypertensive patients. PTCA reverses vasoconstriction by elimination of the flow-limiting stenosis and prevention of coronary stenosis narrowing during exercise in normotensive and hypertensive patients.