Myocardial bridging: what have we learned in the past and will new diagnostic modalities provide new insights?

The clinical significance of myocardial bridging has been a subject of discussion and controversy since the introduction of coronary arteriography (CAG) in the early 1960s. More recently computed tomography coronary angiography (CTCA) has made it possible to visualise the overlying muscular bands and appears to have a higher sensitivity for detecting myocardial bridging than CAG. Combining CTCA with invasive techniques such as CAG should make it possible to improve our understanding of the pathophysiology of myocardial bridging and to provide answers to hitherto unresolved questions. This paper critically reviews the outcomes of previous studies and defines remaining questions that should be answered to optimise the management of the presumably fast growing number of patients in whom a diagnosis of myocardial bridging has been made.

Lipoprotein lipase activity is associated with severity of angina pectoris. REGRESS Study Group.

BACKGROUND: Raised triglyceride-rich lipoproteins significantly increase the risk for cardiovascular disease. Variation in the activity of the enzyme lipoprotein lipase (LPL), which is crucial in the removal of these lipoproteins, may therefore modulate this risk. METHODS AND RESULTS: Postheparin levels of LPL activity and mass were measured in a large cohort of male coronary artery disease patients participating in the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering regression trial. In addition, the relationships between LPL activity and mass and severity of angina pectoris according to the NYHA classification and silent ischemia on 24-hour ambulatory ECG monitoring were assessed. Patients in different LPL activity quartiles and mass had different severities of angina; a total of 47% of patients in the lowest LPL quartile reported class III or IV angina. In contrast, only 29% in the highest activity quartile (P:=0.002) had severe angina. These parameters were supported by ambulatory ECG results, for which the total ischemic burden in the lowest LPL activity quartile was 36. 5+/-104.1 mm x min compared with 14.8+/-38.8 mm x min in the highest quartile of LPL activity (P:=0.001). LPL activity levels were strongly correlated with LPL mass (r=0.70, P:<0.0001). A significant association between the LPL protein mass and NYHA class (P:=0.012) was also demonstrated. CONCLUSIONS: We have demonstrated a significant relationship between LPL mass and activity and severity of ischemia as defined by angina class and ambulatory ECG. These results suggest that LPL influences risk for coronary artery disease by both catalytic and noncatalytic mechanisms.

Arteriographic evaluation of small coronary arteries.

The purpose of this study was to determine the accuracy of imaging small coronary arteries with current radiographic equipment. Phantom assessments were performed using a phantom that comprises a large array of circular objects of varying diameter and contrast density. More objects could be identified in the moving cinearteriogram than in single cine frames. Using the largest object as the calibration standard, diameters less than 1 mm were markedly overestimated. A simple morphometric method showed that arteriographic visualization of small vessels was better by digital processing than by cine recording. However, there was no statistically significant difference in the average size of the smallest identifiable vessel by either method (0.5 versus 0.51 mm). After correcting for overestimation and the inaccurate imaging of the smallest detectable vessels, the practical arteriographic threshold is approximately 0.5 mm. Parametric imaging holds promise, but its significance for evaluating small vessel disease has yet to be determined.

Dobutamine stress magnetic resonance imaging for detection of coronary artery disease.

OBJECTIVES: The clinical value of cine magnetic resonance imaging (MRI) during dobutamine stress for detection of coronary artery disease was evaluated in 45 patients with chest pain who were admitted for coronary arteriography. BACKGROUND: Development of stress-induced wall motion asynergy is considered an early and reliable sign of myocardial ischemia preceding electrocardiographic (ECG) changes and angina. As physical exercise during MRI is difficult because of motion artifacts and space restriction, dobutamine infusion was used to induce cardiovascular stress. METHODS: Cine MRI tomograms were obtained in six adjacent short-axis planes. After baseline acquisition, dobutamine was administered to a maximal dose of 20 micrograms/kg per min. Both at rest and during peak dobutamine stress, magnetic resonance images were displayed in a cinematographic loop to assess regional wall motion qualitatively. Results of dobutamine MRI were considered positive for coronary artery disease if any new or worsening wall motion abnormality developed. Immediately after MRI at peak dobutamine infusion, dobutamine electrocardiography was performed outside the magnetic environment. In addition, all patients performed symptom-limited exercise electrocardiography. RESULTS: Significant coronary artery disease (> 50% diameter stenosis) was present in 37 patients. During peak dobutamine stress, wall motion asynergy developed or worsened in 30 patients, yielding an overall sensitivity for detection of coronary artery disease of 81% and a specificity of 100%. Corresponding data were 51% and 63% for dobutamine electrocardiography and 70% and 63% for exercise electrocardiography. The sensitivity of dobutamine MRI for the detection of coronary artery disease in patients with single-, double- and triple-vessel disease was 75% (15 of 20 patients), 80% (8 of 10) and 100% (7 of 7), respectively. CONCLUSION: Dobutamine MRI is an accurate nonexercise-dependent method for the assessment of myocardial ischemia in patients with coronary artery disease.

Modulation of lipoprotein(a) atherogenicity by high density lipoprotein cholesterol levels in middle-aged men with symptomatic coronary artery disease and normal to moderately elevated serum cholesterol. Regression Growth Evaluation Statin Study (REGRESS) Study Group.

OBJECTIVES: This study sought to examine whether lipoprotein(a) levels predict coronary artery lumen changes in patients with symptomatic coronary artery disease (CAD) and normal to moderate hypercholesterolemia. BACKGROUND: Recent conflicting reports have confirmed or refuted the association of lipoprotein(a) with clinical events or angiographically verified disease progression. METHODS: The association between serum lipoprotein(a) and changes in coronary artery lumen was studied in 704 men entered into the Regression Growth Evaluation Statin Study (REGRESS), a double-blind, placebo-controlled, quantitative angiographic study that assessed the effect of 2 years of pravastatin treatment. The primary end points were changes in average mean segment diameter (MSD) and average minimal obstruction diameter (MOD). Pravastatin- and placebo-treated patients were classified as having progressing, regressing or stable CAD, and median lipoprotein(a) concentrations were compared. Bivariate and multivariate regression analyses were performed in the overall patient group and in high risk subgroups. RESULTS: Pravastatin treatment did not affect serum apolipoprotein(a) levels. Median in-trial (sampled at 24 months) apolipoprotein(a) levels for regressing, stable and progressing CAD were, respectively, 130, 162 and 251 U/liter in placebo-treated patients and 143, 224 and 306 U/liter in pravastatin-treated patients. Predictors of MSD and MOD changes were baseline MSD and MOD, in-trial apolipoprotein(a), in-trial high density lipoprotein (HDL) cholesterol and baseline use of long-acting nitrates. The multivariate models predicted 14% of MSD changes and 12% of MOD changes; apolipoprotein(a) predicted only 2.6% and 4.8%, respectively. However, in patients with in-trial HDL cholesterol levels <0.7 mmol/liter, apolipoprotein(a) predicted up to 37% of the arteriographic changes. CONCLUSIONS: Serum lipoprotein(a) levels predict coronary artery lumen changes in normal to moderately hypercholesterolemic white men with CAD; its atherogenicity is marked in the presence of concomitant hypoalphalipoproteinemia.

Prolonged dilation with an autoperfusion balloon catheter for refractory acute occlusion related to percutaneous transluminal coronary angioplasty.

OBJECTIVES: Efficacy and safety of redilation by an autoperfusion balloon catheter over several hours were investigated in this retrospective and observational study. BACKGROUND: Acute occlusion, refractory to redilation, is a serious complication of coronary angioplasty. METHODS: Of 1,123 patients who underwent angioplasty, 83 had a refractory acute occlusion. Thiry-five patients were treated with extended dilation. Seven had stable, 19 unstable and 6 postinfarction angina and 3 had an acute infarction at the time of angioplasty. The duration of dilation was (mean +/- SD) 17 (+/- 6) h. RESULTS: Angiographically successful redilation, with a mean residual percent diameter stenosis of 13.5% (+/- 11.6%), was achieved in 22 (67.7%) of 34 patients. Five patients underwent bypass surgery. Three patients, who were poor surgical candidates, died. There was one new Q wave infarction and one death that occurred during extended dilation; one death and four operations were related to reocclusion immediately (< or = 30 min) after catheter withdrawal; and one death and one operation were related to in-hospital reocclusion. Overall success, defined as angiographic success and freedom from major events, was obtained in 20 (57%) of 35 patients (95% confidence interval 41% to 73%). Of the variables studied, only multilesion dilation was significantly (p = 0.018) associated with an unfavorable outcome. During a mean follow-up period of 13.8 (+/- 6.1) months, two patients underwent repeat angioplasty, one sustained an infarction and three underwent elective bypass surgery. CONCLUSIONS: In approximately half of the patients (20 [57%] of 35), an initial angioplasty failure due to refractory occlusion could be reverted to a successful procedure by prolonged dilation with an autoperfusion balloon catheter.

B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS).

OBJECTIVES: In this B-mode ultrasound study we assessed pravastatin treatment effects on carotid and femoral artery walls and investigated the correlations between the state and evolution of peripheral and coronary atherosclerosis. BACKGROUND: The Regression Growth Evaluation Statin Study (REGRESS) was an 11-center, 2-year, double-blind, placebo-controlled, prospective study of 885 men with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The study primarily investigated pravastatin treatment effects on the coronary lumen. This report focuses on the 255 patients who participated in the REGRESS ultrasound study. METHODS: Carotid and femoral artery walls were imaged at baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined as the difference in progression of the combined intima-media thicknesses (IMT) between treatment groups. RESULTS: Pravastatin treatment effects were highly significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no individual correlations between IMT and coronary lumen variables (p > 0.30). CONCLUSIONS: Pravastatin treatment effects on carotid and femoral artery walls were observed. B-mode ultrasound imaging studies of peripheral arterial walls could not describe the state and evolution of the coronary lumen in the individual patient, but proved to be a highly suitable tool for the assessment of antiatherosclerotic properties of agents.

Delayed recovery of homogeneous perfusion distribution in isolated rat heart after vasodilatation induced by alpha 1 adrenoceptor blockade during postischaemic reperfusion.

The purpose of this study was to investigate whether vasodilatation induced by doxazosin, an alpha 1 adrenoceptor blocker, during postischaemic reperfusion was able to accelerate reflow in unperfused myocardium. Isolated isovolumetrically beating rat hearts were exposed to global ischaemia by perfusion at 15 mm Hg for 2 h, resulting in an end ischaemic coronary flow rate of 2.3 (SD 1.7)% of preischaemic value, and an unperfused myocardial volume of 71.8(4.3)% of total myocardial volume. Subsequent reperfusion at 80 mm Hg for 2 h produced a partial recovery of coronary flow rate of 41(6)% in the absence of doxazosin and a complete recovery [97(28)%] in the presence of doxazosin 2 mumol.litre-1. Surprisingly, doxazosin induced vasodilatation retarded the disappearance of "no reflow" during reperfusion: after 3 h of reperfusion the volume of unperfused myocardium was 14.3(5.5)% v 1.5(1.7)% in the control group (p less than 0.005). Assessed histologically the regions of "no-reflow" were localised predominantly in the subendocardium. In the presence of doxazosin, left ventricular end diastolic pressure during reperfusion was twice as high as in the control group, indicating pronounced subendocardial compression. The mechanism underlying prolonged subendocardial "no-reflow" in the presence of doxazosin during postischaemic reperfusion is a compressive action of dilated (sub)epicardial vessels on the vasculature in the unperfused subendocardial regions ("hydraulic" or "erectile" effect of increased vascular volume). Thus coronary vasodilatation induced by alpha 1 adrenergic receptor blockade during postischaemic reperfusion delays the recovery of homogeneous transmural perfusion distribution.

Hepatic lipase and lipoprotein lipase are not major determinants of the low density lipoprotein subclass pattern in human subjects with coronary heart disease.

The influence of hepatic lipase (HL) and lipoprotein lipase (LPL) activity on the low density lipoprotein (LDL) subclass pattern was studied in a population of males with coronary heart disease and without severe hypercholesterolemia. LDL subclass patterns, lipases and plasma lipoproteins were determined in 326 patients. In part of the study population, fasting insulin and glucose levels were also determined. The LDL subclass pattern was determined by gradient gel electrophoresis (GGE) and classified according to Austin et al. (J. Am. Med. Assoc. 260 (1988) 1917 (predominantly large LDL = A-pattern, predominantly small LDL = B-pattern). An LDL subclass A-pattern was exhibited by 199 subjects; 108 exhibited a B-pattern. In 19 subjects no distinctive A- or B-pattern was present (A/B-pattern). Hepatic and lipoprotein activities differed significantly between patients with the A- or B-pattern. The median hepatic lipase activity was lower (384 vs. 417 mU/ml, P = 0.006), and the lipoprotein lipase activity higher (122 vs. 101 mU/ml, P = 0.001) in the A-pattern subjects than in the B-pattern subjects. In subjects with the A/B pattern the lipase activities were intermediate between the values in the A- and B-pattern subjects (HL 408 +/- 87 mU/ml, LPL 115 +/- 55 mU/ml). Plasma triglyceride, very low density lipoprotein (VLDL)-triglyceride, intermediate density lipoprotein (IDL)-triglyceride and LDL-triglyceride were higher in the patients with a B-pattern (+84%, +171%, +10% and +16%, respectively). Total plasma cholesterol was not different between A- and B-pattern subjects. VLDL- and IDL-cholesterol were higher in the B-pattern group (+174% and +66%, respectively), while LDL- and HDL-cholesterol were higher in the A-pattern group (+2 and +24%, respectively). In univariate analysis HL, LPL, plasma (and VLDL) triglyceride, HDL-cholesterol and IDL-cholesterol were each significantly associated with the LDL subclass pattern. In multivariate analysis plasma triglyceride (or VLDL-triglyceride) and HDL-cholesterol appeared to be independently associated with the LDL subclass pattern. No additional discriminative value of HL or LPL was found. Similar results were obtained if the patients with or without beta blocker were evaluated separately. An estimate of insulin resistance (EIR), calculated from plasma insulin and glucose in part of the study population (n = 145), was significantly higher in the subjects with a B-pattern than in those with an A-pattern (3.12 vs. 2.00, P < 0.003). EIR correlated positively with plasma triglyceride (P < 0.0001), but not with HL or LPL.(ABSTRACT TRUNCATED AT 400 WORDS)

Raman spectroscopy for quantifying cholesterol in intact coronary artery wall.

The chemical composition of vascular lesions, an important determinant of plaque progression and rupture, can not presently be determined in vivo. Prior studies have shown that Raman spectroscopy can accurately quantify the amounts of major lipid classes and calcium salts in homogenized coronary artery tissue. This study determines how the relative cholesterol content, which is calculated from Raman spectra collected at the luminal surface of an artery, is related to its depth in an intact arterial wall. Raman spectra of human atherosclerotic plaques were measured after thin tissue layers were successively placed on them. From these spectra, relative cholesterol contents were calculated and used to determine how cholesterol signal strength is attenuated by overlaying tissue. Then, intact artery samples (n = 13) were examined spectroscopically, sectioned and stained specifically for cholesterol. Images of these sections were digitized, and image intensities were related to cholesterol content. These cholesterol amounts were weighed appropriately for depth into the tissue and area-integrated for comparison with spectroscopy results. A decaying exponential curve was fit to the layer study data (r2 = 0.97) and showed that approximately 300 microm of tissue attenuates cholesterol signals by 50%. In intact plaques, the spectroscopically-determined cholesterol amounts correlated strongly and linearly with those determined by digital microscopy (r2 = 0.94). With Raman spectroscopy techniques, the cholesterol content of a lesion can be determined by properly accounting for its depth into an arterial wall. Our results suggest that chemical concentrations in an artery wall could be mapped throughout its thickness, possibly by combining Raman spectroscopy methods with other techniques.

Cognitive-behavioral therapy for noncardiac chest pain: a randomized trial.

PURPOSE: Patients with nonischemic chest pain frequently experience recurrent symptoms, have persistent functional and occupational disability, and are high utilizers of health-care resources. Our aim was to evaluate the efficacy of a cognitive-behavioral treatment for patients with noncardiac chest pain. PATIENTS AND METHODS: Subjects were recruited from patients with at least weekly episodes of noncardiac chest pain, as diagnosed by a cardiologist. The main outcome measures were frequency and intensity of chest pain at 6 and 12 months. RESULTS: Seventy-two patients were enrolled in the study; 37 were assigned to cognitive-behavior therapy and 35 to usual care. Sixty-five patients completed the study. Intervention patients improved significantly with regard to frequency and intensity of chest pain: 15 (48%) of the 31 patients in the treatment group were pain free at 12-month follow-up compared with 4 (13%) of the 33 patients in the control group (P = 0.002). CONCLUSIONS: Cognitive-behavioral therapy for noncardiac chest pain patients was effective compared with usual care.

The importance of high-frequency paced breathing in spectral baroreflex sensitivity assessment.

OBJECTIVE: Computation of the low-frequency (LF) blood pressure variability (BPV) to heart rate variability (HRV) transfer-index is a common method to assess baroreflex sensitivity (BRS), tacitly assuming that all LF-HRV is caused by baroreflex feedback of LF-BPV. However, respiration may also cause HRV by mechanisms not involving the baroreflex. Application of narrow-band (controlled) high-frequency breathing would keep such non-baroreflex-mediated HRV best out of the LF band. Spontaneous breathing, because of its broad-band character, might cause extra, non-baroreflex-mediated, HRV in the LF band, while paced LF breathing would even concentrate most non-baroreflex-mediated HRV in the LF band. Our study addresses the likely resulting BRS overestimation. DESIGN: We recorded HRV and BPV in 20 healthy young subjects in the sitting position. We varied the sympathovagal balance by gradual leg-lowering from horizontal till 60 degrees . At each angle the subjects performed controlled 0.10 Hz, spontaneous, and controlled 0.25 Hz respiration. RESULTS: Resting BRS values were 15.5(7.2), 13.1 (3.7), and 11.6(6.2) ms/mmHg, respectively. Both the 15/min and the free breathing values differed significantly, P< 0.01 and P= 0.04, from the 6/min breathing value. With lowered legs, the BRS values were 8.2(3.4), 8.3(2.9), and 8.3(3.4) ms/mmHg, respectively. CONCLUSION: Controlled 6/min breathing caused significant BRS overestimation under resting conditions. For the group, spontaneous respiration yielded acceptable BRS values, but individual BRS values deviated sometimes considerably. Conversely, with gravitational load, the respiratory pattern had only minor impact on BRS. Our results demonstrate that the risk of an overestimated BRS value is realistic as long as respiration is not controlled and of high-frequency.

Similar orthostatic defense in active, healthy young adult and late middle-aged men.

Orthostatic defense is commonly validated with a 60 degrees to 80 degrees head-up tilt test, addressing the step response rather than the response to permanent orthostatis. During the initial phase of tilt, neural factors predominate, while later, the slower humoral factors fade in. It has been demonstrated that, during adaptation of the circulatory system to the standing conditions, overshoot and undershoot occur. These oscillations hamper straight-forward interpretation of a tilt test, and may contribute to the inconclusiveness of current studies regarding the aging of orthostatic defense. Gradual, progressive, orthostatic load testing seems a valuable alternative. We used a novel, incremental, head-up tilt protocol (0 degrees to 80 degrees, 13 increments) to impose graded orthostatic stress on 46 healthy young adult men (mean age +/- SD 25 +/- 3 years), and on 16 healthy late middle-aged men (60 +/- 4 years), while recording the electrocardiogram and the blood pressure. A first-order estimate of the heart rate range associated with the sympathovagal transition was made by combined analysis of heart rate and heart rate variability trends. We observed similar responses in heart rate, heart rate variability, and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral cardiac myxomas and peripheral myxomas in a patient with recent myocardial infarction.

Coronary arteriography, performed for recent anterior wall myocardial infarction in a 29 year old man, showed multiple aneurysms of the distal branches of the left coronary artery without evidence of obstructions in the major branches, and two clusters of abnormal vessels, supplying tumors in the right ventricle and the left atrium. At operation and histologic examination both tumors appeared to be myxomas. In addition, two myxomas, located elswhere in the body, could be proven histologically.

Silent myocardial ischemia after acute myocardial infarction.

Silent ischemia after myocardial infarction has definite prognostic significance but should be interpreted within the context of other prognostic indicators. The rationale for therapeutic intervention is based on the prognostic implications of silent ischemia and the potentially deleterious effect of repeated episodes of ischemia on the integrity of the left ventricle. We measured parameters of ischemia in 20 patients who showed asymptomatic ischemic ST-T changes on exercise testing in the early phase after myocardial infarction. After diltiazem administration, a reduction of exercise-induced ST-T depression from 2.3 +/- 0.8 to 0.7 +/- 0.6 mm (p less than 0.01) occurred, and regional wall-motion score at exercise, determined by radionuclide angiography, improved significantly (p less than 0.02). These and other observations warrant further studies in which the duration, severity and frequency of the ischemic episodes should be quantified and correlated with prognosis after myocardial infarction.

Usefulness of ultrafast magnetic resonance imaging in healed myocardial infarction.

The value of ultrafast magnetic resonance imaging (MRI) in the assessment of dynamic contrast enhancement and myocardial perfusion abnormalities was evaluated in 20 patients with healed myocardial infarction, who also underwent 2-dimensional echocardiography. At baseline and after bolus injection of the paramagnetic contrast agent gadolinium-diethylenetriaminepentaacetic acid (DTPA) (0.04 mmol/kg body weight), single-level short-axis MRI was performed every third RR interval with an acquisition time of 500 ms. Myocardial signal intensities were measured in transmural myocardial regions of interest. After gadolinium-DTPA injection, infarcted and normal myocardium demonstrated a signal intensity enhancement of 50 and 134%, respectively (p < 0.001). A signal intensity of normal relative to infarcted myocardium increased from 1.25 +/- 0.22 (SD) before to 1.91 +/- 0.41 after gadolinium-DTPA (p < 0.001). The rate of signal increase in the infarcted and normal myocardium was 5.17 +/- 2.22 and 18.99 +/- 9.96 s-1 (p < 0.001), respectively. Ultrafast MRI using gadolinium-DTPA bolus administration clearly identifies myocardial perfusion abnormalities in patients with healed myocardial infarction. The infarct site on MRI corresponded with the location of wall motion asynergy determined by echocardiography. It is concluded that gadolinium-DTPA-enhanced ultrafast MRI provides noninvasive assessment of myocardial perfusion in patients with proven coronary artery disease.

Pravastatin reduces restenosis two years after percutaneous transluminal coronary angioplasty (REGRESS trial).

The Regression Growth Evaluation Statin Study (REGRESS) is a placebo-controlled multicenter study designed to assess the effect of 2-year treatment with pravastatin on the progression and regression of angiographically documented coronary artery disease. One of the secondary end points was the occurrence of 2-year restenosis in the percutaneous transluminal coronary angioplasty (PTCA) block. We randomly assigned eligible patients to receive pravastatin 40 mg once daily or placebo. The end point was the percent diameter stenosis of the target lesion at 24 months, as assessed by (semi)quantitative coronary angiography. Two hundred twenty-one patients underwent scheduled PTCA, which was considered successful in 201 patients. One hundred seventy-eight patients underwent angiographic restudy (89%). The patients in the pravastatin group (n = 109) and placebo group (n = 112) were similar at baseline. Percent diameter stenosis before angioplasty was 78 +/- 14% (mean +/- SD) in the pravastatin group and 80 +/- 14% in the placebo group (p = 0.46). At follow-up, the percent diameter stenosis was 32 +/- 23% in the pravastatin group and 45 +/- 29% in the placebo group (p < 0.001). Clinical restenosis was significantly lower in the pravastatin group (7%) compared with the placebo group (29%) (p < 0.001). Risk reduction for all events was 58%. We conclude that treatment with pravastatin reduces 2-year clinical and angiographic restenosis.

Effect of pravastatin on progression and regression of coronary atherosclerosis and vessel wall changes in carotid and femoral arteries: a report from the Regression Growth Evaluation Statin Study.

Few data are available about the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels. REGRESS is a double-blind, placebo-controlled, multicenter study to assess the effect of a 2-year treatment with the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis using quantitative coronary arteriography in 885 male patients with a total serum cholesterol value of 155-310 mg/dl (4-8 mmol/liter). Among symptomatic men with significant coronary atherosclerosis and normal to moderately raised levels of serum cholesterol, patients treated with pravastatin had less progression of coronary atherosclerosis and fewer new cardiovascular events than patients in the placebo group. Ultrasound examinations of carotid and femoral arteries were performed in 255 patients. Changes in intimal-medial thickness also showed a treatment effect from pravastatin; however, on a per patient basis, there was no correlation with the treatment effect in the coronary arteries.

Clinical and angiographic outcome of Micro Stent II implantation in native coronary arteries.

To evaluate immediate success and 6-month restenosis rate, 70 Micro Stents II were implanted for 65 stenoses in 63 patients (age 59+/-9 years). Stable angina pectoris was present in 47% of the patients (38% class I to III; 9% class IV), whereas 32% had postinfarction angina and 21% had unstable angina. Indications for stent implantation were elective in 62% and semi-elective in 38% of the patients. Sixty-two percent of the patients received ticlopidin and acetylsalicylic acid for 28 days, whereas 38% of the patients received only acetylsalicylic acid. All stents were deployed successfully at the target site. Subacute closure occurred in 2 patients (3%), both of whom were not treated with ticlopidin. Two other patients (3%) developed non-Q-wave infarction after side branch occlusion during the procedure. The minimum lumen diameter increased from 1.0+/-0.5 mm to 2.8+/-0.4 mm after stent implantation. At follow-up the loss in diameter was 0.9+/-0.6 mm, indicating a net gain of 0.9+/-0.8 mm. Late clinical events (4 weeks to 6 months) were coronary angioplasty of a stented segment (3%), coronary angioplasty of a nonstented segment (10%), and coronary artery bypass grafting (2%). No deaths or myocardial infarction occurred. The procedural success rate was 94% and the event-free survival at 6-month follow-up was 79%. Micro Stent II implantation can be done with a high rate of immediate success and good 6-month outcome. The Micro Stent II has proven to be a versatile device that can also be used in patients with less favorable coronary anatomy or lesion characteristics.

Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary atherosclerosis and restenosis.

It has proved difficult to identify high-risk patients for atherosclerosis and to determine how they might respond to medication. Recently, a common promoter variant of the human stromelysin-1 gene has been reported, which has been shown to affect the transcription. We investigated whether this polymorphism had any impact on the risk of events, especially restenosis and progression of coronary artery disease and whether the effect was modulated by treatment with pravastatin. The stromelysin-1 genotype was determined for 496 men with coronary artery disease and cholesterol levels between 4.0 and 8.0 mmol/L, participating in the Regression Growth Evaluation Statin Study (REGRESS) study, a clinical trial assessing the effect of the lipid-lowering drug pravastatin on the progression of atherosclerosis. Patients in the placebo group with 5A6A or 6A6A genotypes had more clinical events than patients with the 5A5A genotype (26% and 12%, respectively, p = 0.03). In the pravastatin group, the risk of clinical events in patients with 5A6A or 6A6A genotypes was lower, compared with placebo, whereas it was unchanged in those with a 5A5A genotype (p value for interaction: 0.038). Also, the incidence of repeat angioplasty in the placebo group was greater in patients with the 6A6A or 5A6A genotypes, compared with 5A homozygotes (38% and 40%, respectively, vs 11%, p = 0.09). Again, treatment substantially reduced the incidence in heterozygotes and 6A homozygotes (0% and 15%, respectively), whereas it was unchanged in 5A homozygotes (28%, p for interaction: 0.002). These effects were independent of the effects of pravastatin on the lipid levels. Thus, this study suggests that the stomelysin-1 promoter polymorphism confers a genotype-specific response to medication in determining clinical event-free survival and the risk for symptom-driven repeat angioplasty. This variant may therefore act as a predictor, not only of disease progression, but also of response to therapy and risk of restenosis.