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This study evaluated patients in the Post Coronary Artery Bypass Graft (Post CABG) trial for evidence of statin pleiotropic effects in preventing atherosclerotic progression in saphenous vein grafts (SVGs). We studied 1,116 of the 1,351 patients in the Post CABG trial who were randomized to aggressive (low-density lipoprotein [LDL] cholesterol target <85 mg/dl) or moderate (target LDL cholesterol <140 mg/dl) lovastatin treatment and who had sufficient data available. The generalized estimating equation models, adjusting for important covariates, were applied to estimate the odds ratios (ORs) and probability of substantial atherosclerotic SVG progression (decrease in lumen diameter >or=0.6 mm) and the difference in minimum lumen diameter change between treatment groups. Aggressive lovastatin treatment compared with moderate treatment was associated with a significant decrease in risk of significant SVG atherosclerotic progression after adjustment for baseline cholesterol level, LDL cholesterol on treatment, high-density lipoprotein cholesterol, and triglyceride changes on treatment and other independent predictors (OR 0.68, 95% confidence interval 0.49 to 0.94, p = 0.019). Results were similar when the change or percent change from baseline of LDL cholesterol level on treatment was adjusted for rather than on-treatment LDL cholesterol and in the subset achieving a year-1 LDL cholesterol level from 90 to 135 mg/dl (OR 0.64, 95% confidence interval 0.42 to 0.98, p = 0.042). Mean decrease in minimum lumen diameter was also significantly smaller in the aggressive than the moderate treatment arm (-0.256 vs -0.343 mm, p = 0.042). In conclusion, aggressive versus moderate lovastatin treatment appeared therapeutic in slowing the atherosclerotic process in SVGs from Post CABG patients, independent of its greater LDL cholesterol-lowering effect.

Background: Prior randomized trials suggested that revascularization of diabetic patients by coronary artery bypass grafting (CABG) produced results superior to balloon angioplasty. The introduction of drug-eluting stents (DESs) calls into question the relevance of past studies to the current era. The FREEDOM Trial is designed to determine whether CABG or percutaneous coronary intervention (PCI) is the superior approach for revascularization of diabetic patients., Study Design: The FREEDOM Trial is a multicenter, open-label prospective randomized superiority trial of PCI versus CABG in at least 2000 diabetic patients in whom revascularization is indicated. Consenting diabetic patients with multivessel disease will be randomized on a 1:1 basis to either CABG or multivessel stenting using DESs and observed at 30 days, 1 year, and annually for up to 5 years. At the discretion of the primary physician or interventionalists, patients randomized to the PCI/DES arm will receive any approved DESs. The primary outcome measure is the composite of all-cause mortality, nonfatal myocardial infarction, or stroke. Patients will be observed for a mean of 4 years., Implications: At present, coronary revascularization with CABG surgery is the treatment of choice in diabetic patients with multivessel coronary artery disease. Drug-eluting stents have shown promising preliminary results in the diabetic population. The FREEDOM Trial is an international study designed to define the optimal revascularization strategy for the diabetic patient with multivessel coronary disease.

Background: Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and the risks for death and cardiovascular events among patients with stable coronary disease., Methods and Results: We studied patients enrolled in the Prevention of Events with an ACE inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed up for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate and outcomes. The majority of patients (73%) had a baseline ACR within the normal range (<17 mug/mg for men and <25 mug/mg for women). Independent of the estimated glomerular filtration rate and other baseline covariates, a higher ACR, even within the normal range, was associated with increased risks for all-cause mortality (P<0.001) and cardiovascular death (P=0.01). The effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 versus 14.6 mug/mg, P=0.0002), after adjustment for baseline ACR, time between collections, and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (hazard ratio per log ACR 1.74, 95% CI 1.08 to 2.82)., Conclusions: Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.

Arterial stiffness, as evidenced by increased pulse pressure (PP), is associated with adverse cardiovascular events. However, the prognostic importance of PP in patients who have undergone revascularization is unknown. We examined the prognostic importance of PP and predictors of increased PP in patients entered into the Balloon Angioplasty Revascularization Investigation (BARI). Estimated correlation and standardized regression coefficients were reported, indicating the relative magnitude of independent effects of baseline characteristics on PP. The independent association of PP and outcome over 5 years was determined. Baseline characteristics independently associated with PP were higher mean arterial pressure, older age, female sex, noncoronary vascular disease, history of diabetes mellitus, and history of hypertension (p <0.001 for all). Cox regression covariates significantly associated with time to death were age, smoking, male gender, diabetes history, congestive heart failure, and baseline use of angiotensin-converting enzyme inhibitors, diuretic, or digitalis. When PP was added to the model, it was found to be an independent predictor of time to death (p = 0.008). When PP and mean arterial pressure were added to the model, PP remained significantly associated with time to death (p = 0.033). When renal disease and noncoronary vascular disease were added to the model, the relative risk declined from 1.07 to 1.04 and the association was no longer statistically significant. Thus, increased PP is directly and independently associated with mean arterial pressure, hypertension, age > or =65 years, diabetes mellitus, and the presence of noncoronary vascular disease, and inversely associated with a history of myocardial infarction. After coronary revascularization, PP, reflecting arterial stiffness, is independently associated with total mortality.

The reported results (The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. New Engl J Med 1997;336:153-162) of the Post Coronary Artery Bypass Graft (Post CABG) trial have shown that aggressive lowering was more effective than moderate lowering of low density lipoprotein (LDL) cholesterol in reducing the progression of atherosclerosis in saphenous-vein grafts (27 vs. 39%; P < 0.001); low dose warfarin had no effect on the progression of atherosclerosis. The present report describes the effect of long-term (an average of 4.3 years) aggressive treatment with high (40-80 mg/day) and moderate treatment with low (2.5-5 mg/day) doses of lovastatin on lipids, apolipoproteins (apo) and apoA- and apoB-containing lipoprotein families. To achieve the target LDL-cholesterol levels (60-85 mg/dl for aggressive group and 134-140 mg/dl for moderate group), cholestyramine (8 g/day) was given to 25% of subjects on aggressive and 5% of subjects on moderate treatment. Although with both treatment strategies there were significant decreases (P<0.001) in the levels of total cholesterol, LDL-cholesterol, apoB, LDL-apoB and cholesterol-rich Lp-B family, percent changes in the levels of these variables were greater in the aggressive- than in the moderate-treatment groups. These treatments had only marginal effects in increasing the levels of high density lipoprotein cholesterol, apoA-I and Lp-A-I and Lp-A-I:A-II families. The long-term aggressive treatment exerted no effect on the concentrations of triglycerides, apoC-IlI, apoC-III in VLDL + LDL and triglyceride-rich Lp-Bc families. Neither treatment affected the levels of Lp(a). The potentially modifying influence of warfarin and apoE phenotypes on lovastatin-induced changes in lipoprotein variables was found to be of little significance. It is likely that the beneficial effect of lovastatin in reducing the progression of atherosclerosis in grafts is mediated through its specific lowering effect on cholesterol-rich Lp-B particles.

Background: The NHLBI Post Coronary Artery Bypass Graft trial (Post CABG) showed that aggressive compared with moderate lowering of low-density lipoprotein-cholesterol (LDL-C) decreased obstructive changes in saphenous vein grafts (SVGs) by 31%.1 Using lovastatin and cholestyramine when necessary, the annually determined mean LDL-C level ranged from 93 to 97 mg/dL in aggressively treated patients and from 132 to 136 mg/dL in the others (P<0.001)., Methods and Results: The present study evaluated the treatment effect in subgroups defined by age, gender, and selected coronary heart disease (CHD) risk factors, ie, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C) <35 mg/dL, and triglyceride serum levels >/=200 mg/dL at baseline. As evidenced by similar odds ratio estimates of progression (lumen diameter decrease >/=0.6 mm) and lack of interactions with treatment, a similar beneficial effect of aggressive lowering was observed in elderly and young patients, in women and men, in patients with and without smoking, hypertension, or diabetes mellitus, and those with and without borderline high-risk triglyceride serum levels. The change in minimum lumen diameter was in the same direction for all subgroup categories, without significant interactions with treatment., Conclusions: Aggressive LDL-C lowering delays progression of atherosclerosis in SVGs irrespective of gender, age, and certain risk factors for CHD.

A substantial number of patients present with medically refractory angina who are not candidates for angioplasty or bypass surgery. The creation of channels between the myocardium and the ventricular blood pool has been performed after thoracotomy with excellent relief of symptoms but has been associated with high perioperative mortality. We investigated the safety of a nonoperative, percutaneous technique for channel creation. Twenty-seven patients with angina and coronary anatomy not amenable to revascularization with coronary angioplasty or bypass surgery underwent percutaneous transluminal myocardial revascularization (PTMR). Energy from a Holmium:yttrium-aluminum-garnet (YAG) laser was directed through a fiber enclosed in a catheter to the ventricular myocardium creating channels between the blood pool and the myocardium. On average, 17 +/- 4 channels were formed per patient. There were no procedure-related deaths, episodes of tamponade, or other complications except for an increase in creatine phosphokinase in 1 patient. Immediately after the procedure, there was no worsening of regional wall motion function in any patient, but rather improvement in some. All patients were discharged alive after a hospital stay of 1.8 +/- 1.5 days. Mean Canadian Cardiovascular Society functional class declined from 3.6 +/- 0.5 before the procedure to 0.65 +/- 0.8 at 30 days after the procedure (p < 0.01). For 12 patients eligible for 6-month follow-up, mean functional class was 0.94 +/- 0.97. At 6-month stress testing, 9 of these 12 had no electrocardiographic evidence of ischemia. Thus, PTMR can be performed safely in the cardiac catheterization laboratory with a complication rate lower than that reported in surgical series and with excellent near-term symptomatic relief. The long-term effect of PTMR on mortality and relief of angina as well as its safety and effectiveness compared with the surgical approach remains to be defined.

The Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) trial is an 8,100 patient, randomized, double-blind, placebo-controlled trial designed to determine the usefulness of angiotensin-converting enzyme (ACE) inhibitors in treating coronary patients with preserved left ventricular ejection fraction. The hypothesis being tested in this trial is that patients with coronary disease and ejection fraction > or =40% who are treated with ACE inhibitors will experience a reduction in the incidence of cardiovascular death, nonfatal myocardial infarction, or a revascularization procedure compared with patients treated with conventional therapy. The design of the PEACE trial is described herein.

Fifty-one consecutive patients in whom percutaneous cardiopulmonary bypass support was instituted to enhance the safety of high-risk elective coronary angioplasty were studied. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the target artery(s) or both. Thirty-five men and 16 women, mean age 63 years, with Canadian Cardiovascular Society class III angina (23 patients) or class IV (28 patients) were studied. There was a history of myocardial infarction in 45 (88%), bypass surgery in 14 (27%) and congestive heart failure in 17 (33%). Forty-six (90%) had impaired left ventricular function. Twenty (39%) had an ejection fraction of less than or equal to 25%. Left main stenosis was present in 9 (18%), 3-vessel disease in 48 (94%) and 2-vessel disease in 2 (4%). Twenty (39%) were considered at a prohibitive risk for bypass surgery (14 were turned down for surgery). Bypass was instituted percutaneously with flows ranging from 2 to 5 liters/min (mean 3.6). Angioplasty was successful in 115 of the 117 lesions attempted with the culprit vessel dilated in all. Dilatation of the only remaining vessel was performed in 14 (27%). Inflation times up to 10 minutes were well tolerated. Bypass was discontinued after a mean bypass time of 37 minutes. Hemostasis was achieved by external clamp compression in 50. There were 3 hospital deaths unrelated to bypass. Patient follow-up at 2 to 8 months (mean 4.9) disclosed 1 late death, 31 (66%) asymptomatic patients, 12 (26%) patients in class I and 4 patients (9%) in class II. Thus, this study demonstrates the safety and efficacy of percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty.

We conducted a retrospective analysis of the Studies Of Left Ventricular Dysfunction (SOLVD) trials to assess the predictive value of the baseline white blood cell (WBC) count on mortality. Mortality was higher in participants with a baseline WBC count >7,000 compared to those with a baseline WBC < or =7,000 (27% vs 21%, p <0.0001). After controlling for important covariates, each increase in WBC count of 1,000/mm3 was significantly associated with an increased risk of all-cause mortality (relative risk [RR] 1.05, p <0.001). Overall, compared with a baseline WBC count < or =7,000, a baseline WBC count >7,000 was significantly associated with an increased risk of all-cause mortality (RR 1.22, p = 0.001). In participants with ischemic left ventricular (LV) dysfunction, a WBC count >7,000 remained significantly associated with an increased risk of all-cause mortality (RR 1.26, p <0.001), whereas in participants with nonischemic LV dysfunction there was no relation between WBC count and mortality (RR 1.08, p = 0.5). Thus, baseline WBC is an independent predictor of mortality in patients with LV dysfunction, specifically in those with ischemic cardiomyopathy. [ABSTRACT FROM AUTHOR]