Benefits of lipid lowering on vascular reactivity in patients with coronary artery disease and average cholesterol levels: a mechanism for reducing clinical events?

BACKGROUND: The favorable effects of lowering low-density lipoprotein (LDL)-cholesterol on reducing clinical events in patients with coronary disease have been well established. The mechanisms responsible for this benefit, however, have not been fully understood. This study examined the impact of lipid-lowering therapy on endothelium-dependent vasoreactivity in a subgroup of patients after myocardial infarction with average cholesterol levels who participated in the Cholesterol Recurrent Events (CARE) study to determine whether an effect on endothelial function is a viable mechanism for the observed reduction in clinical events. METHODS AND RESULTS: Participants were recruited from among volunteers in the CARE trial at 2 university-based outpatient cardiology clinics. Patients were randomly assigned to pravastatin or placebo. Plasma lipids were measured at baseline and semiannually thereafter. During the final 6 months of the trial, vasoreactivity was assessed by change in ultrasound-determined brachial artery diameter in response to blood pressure cuff-induced ischemia (endothelium-dependent) and to nitroglycerin, a direct vasodilator. Differences in response were examined between the 2 randomized groups. The relation between change in LDL-cholesterol from baseline to year 5 and the magnitude of endothelium-dependent vasodilation also was examined. There was significantly greater endothelium-dependent vasodilation observed in the pravastatin group compared with the placebo group (13% vs 8%, P =.0002), with no difference between the groups in their response to the endothelium-independent vasodilator nitroglycerin. The magnitude of the endothelium-dependent vasodilation was significantly correlated with the percent change in LDL-cholesterol from baseline to final visit (r = 0.49, P =.015). CONCLUSIONS: These findings indicate that the use of pravastatin in patients after myocardial infarction with average cholesterol levels is associated with greater endothelium-dependent vasodilation compared with those who received placebo. The magnitude of this vasodilatory response is correlated to the reduction in LDL-cholesterol. This improvement in endothelium-dependent vasoreactivity may be a likely mechanism, at least in part, for the reduction in recurrent clinical events observed and reported in the CARE study.

Heterogeneity of coronary flow reserve in the examination of multiple individual allograft coronary arteries.

BACKGROUND: Epicardial and resistance vessel function in the transplanted heart has been evaluated primarily in regions supplied by a single vessel. Heterogeneity of flow among multiple perfusion fields as a marker of early endothelial dysfunction in the microcirculation has not been evaluated previously. This study tested the hypothesis that increased variability of coronary flow reserve (CFR) among multiple vascular regions would be associated with allograft coronary vasculopathy. METHODS AND RESULTS: One hundred six posttransplant patients undergoing cardiac catheterization had measurement of CFR in at least 3 major epicardial vessels. Patients were divided into those with minimal angiographic abnormalities (n=37) and those with no angiographic abnormalities (n=69). The ranges, coefficients of variation, and univariate and multivariate regression analyses of CFR were computed to determine the major clinical factors influencing the degree of variability. The abnormal angiographic group was older (54+/-11 versus 47+/-13 years; P<0.003), had older hearts (35+/-11 versus 27+/-10 years; P<0.005), and were further posttransplant (1626+/-1022 versus 931+/-984 days; P<0.0009). There was no difference in global CFR between groups (normal, 3.4+/-0.8 versus abnormal, 3.4+/-0.7; P=NS). The coefficient of variation of CFR was higher for the abnormal group (16.3+/-8.6% versus 11.0+/-5.5%; P<0. 0006). Univariate and multivariate predictors of increased variability in CFR included angiographic abnormalities, patient age, and body mass index. Both angiographic abnormalities and an elevated CV of CFR were predictive of a combined end point of death, congestive heart failure, or subsequent development of >/=50% coronary stenosis. CONCLUSIONS: These data demonstrate that increased variability of CFR is associated with discernible allograft coronary arteriopathy and is predictive of outcome in patients after heart transplantation.

Role of coronary artery lumen enlargement in improving coronary blood flow after balloon angioplasty and stenting: a combined intravascular ultrasound Doppler flow and imaging study.

OBJECTIVES: This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting. BACKGROUND: Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in > or = 50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results. METHODS: To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity. RESULTS: The percent diameter stenosis decreased from (mean +/- SD) 84 +/- 13% to 37 +/- 18% after angioplasty and to 8 +/- 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 +/- 0.79 at baseline to 1.89 +/- 0.56 (p = NS) after angioplasty but increased to 2.49 +/- 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 +/- 2.09 vs. 5.10 +/- 2.03 mm2, p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001). CONCLUSIONS: In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.